bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Materials and Methods, Figures and Tables from A Targeted Quantitative Proteomic Approach Assesses the Reprogramming of Small GTPases during Melanoma Metastasis
Authors: Huang Ming , Qi Tianyu F. , Li Lin , Zhang Gao , Wang Yinsheng
Published: March 2023

I. Supplementary Figures Figure S1. LC-MRM-based targeted quantitative proteomic assay revealed differential expression of small GTPases during melanoma metastasis. Figure S2. The scheduled LC-MRM platform provides accurate retention time (RT) prediction of targeted peptides, high sensitivity and excellent reproducibility. Figure S3. Validation of RAB32 expression in WM-115/WM-266-4 and IGR39/IGR37 paired melanoma cell lines. Figure S4. RAB12 and RAB31 were differentially expressed in WM-115 and WM-266-4 cells. Figure S5. Western blots confirmed the overexpression and knockdown of RAB38 in WM-115 and WM-266-4 cells, respectively. Figure S6. RAB38 mediates both the expression levels and activities of MMP2 and MMP9 in metastatic IGR37 and M14 cells. Figure S7. Correlations of mRNA expressions of MITF, RAB38 and RAB27A with different genetic backgrounds of melanoma patients. Figure S8. Up-regulation of MITF in metastatic melanoma cells. Figure S9. RAB38 expressions were highly correlated with MITF in a large number of melanoma cell line and melanoma patient cohorts. Figure S10. Higher levels of expression of RAB38 in metastatic melanoma compared to primary melanoma were observed in melanoma patient with MITF high signature. Figure S11. Occurrence and prognostic values of RAB38 promoter hypomethylation. II. Supplementary Methods and Materials 1) Sample Preparation and LC-MS/MS for Shotgun Proteomic Analysis. 2) Retention time (RT) Prediction for Small GTPase Peptides. 3) Sample Preparation and Scheduled LC-MRM Analysis. 4) Construction and Transfection of FLAG-tagged Fusion Protein Expression Plasmid. 5) siRNA Transfection. 6) Real-time Quantitative PCR (RT-qPCR). III. Supplementary Tables Table S1. A complete list of primers used for real-time quantitative PCR (RT-qPCR) in this study. Table S2. A complete list of small GTPases of the Ras superfamily in the human proteome. Table S3A. A complete list of small GTPases in the Skyline MRM library with their gene names, IPI numbers, and targeted peptides and transitions. 4) Table S3B. A complete list of quantified small GTPase peptides and proteins in three sets of SILAC experiments for WM, IGR and WMLu paired melanoma cell lines.
Supplementary Table 5 from SETD2 Is Recurrently Mutated in Whole-Exome Sequenced Canine Osteosarcoma
Authors: Sakthikumar Sharadha , Elvers Ingegerd , Kim Jaegil , Arendt Maja L. , Thomas Rachael , Turner-Maier Jason , Swofford Ross , Johnson Jeremy , Schumacher Steven E. , Alföldi Jessica , Axelsson Erik , Couto C. Guillermo , Kisseberth William C. , Pettersson Mats E. , Getz Gad , Meadows Jennifer R.S. , Modiano Jaime F. , Breen Matthew , Kierczak Marcin , Forsberg-Nilsson Karin , Marinescu Voichita D. , Lindblad-Toh Kerstin
Published: March 2023

File contains genes that have focal somatic copy number deletions.
Supplementary Figures 1-8 from SETD2 Is Recurrently Mutated in Whole-Exome Sequenced Canine Osteosarcoma
Authors: Sakthikumar Sharadha , Elvers Ingegerd , Kim Jaegil , Arendt Maja L. , Thomas Rachael , Turner-Maier Jason , Swofford Ross , Johnson Jeremy , Schumacher Steven E. , Alföldi Jessica , Axelsson Erik , Couto C. Guillermo , Kisseberth William C. , Pettersson Mats E. , Getz Gad , Meadows Jennifer R.S. , Modiano Jaime F. , Breen Matthew , Kierczak Marcin , Forsberg-Nilsson Karin , Marinescu Voichita D. , Lindblad-Toh Kerstin
Published: March 2023

Supplementary Figure 1 - Workflow for Somatic Point and Indel Mutation detection. Supplementary Figure 2 - Heatmap counts of samples with recurrent focal SCNAs per chromosome. Supplementary Figure 3 - oaCGH profiles penetrance plots and GISTIC analysis. Supplementary Figure 4 - Venn diagrams of shared and unique somatic point mutations and somatic indel mutations across the three breeds. Supplementary Figure 5 - Scatter plot shows age of diagnosis is positively correlated to the mutation counts across all breeds. Supplementary Figure 6 - Mutational signature distribution per breed shows enrichment for the novel signature in Golden Retriever. Supplementary Figure 7 - Overview and functional classes for the mutations in histone modifier genes across the three breeds. Supplementary Figure 8 - Overview of germ-line candidate mutation across three breeds and their functional impacts.
Figure S4 from Oncogenic Kinase–Induced PKM2 Tyrosine 105 Phosphorylation Converts Nononcogenic PKM2 to a Tumor Promoter and Induces Cancer Stem–like Cells
Authors: Zhou Zhifen , Li Min , Zhang Lin , Zhao Hong , Şahin Özgür , Chen Jing , Zhao Jean J. , Songyang Zhou , Yu Dihua
Published: March 2023

Activation of YAP downstream signaling is important for pY105-PKM2-induced cancer stem-like properties.
Figure S2 from Oncogenic Kinase–Induced PKM2 Tyrosine 105 Phosphorylation Converts Nononcogenic PKM2 to a Tumor Promoter and Induces Cancer Stem–like Cells
Authors: Zhou Zhifen , Li Min , Zhang Lin , Zhao Hong , Şahin Özgür , Chen Jing , Zhao Jean J. , Songyang Zhou , Yu Dihua
Published: March 2023

PKM2 is highly phosphorylated at Y105 in mammary tumors from MMTV-neu mice.
Supplementary Tables from High USP6NL Levels in Breast Cancer Sustain Chronic AKT Phosphorylation and GLUT1 Stability Fueling Aerobic Glycolysis
Authors: Avanzato Daniele , Pupo Emanuela , Ducano Nadia , Isella Claudio , Bertalot Giovanni , Luise Chiara , Pece Salvatore , Bruna Alejandra , Rueda Oscar M. , Caldas Carlos , Di Fiore Pier Paolo , Sapino Anna , Lanzetti Letizia
Published: March 2023

S1-Prognostic value of USP6NL gain in the METABRIC dataset S2-Correleation of USP6NL protein expression with clinical-pathological parameters in the TMA cohort
Supplementary Figures with legends from SATB2-AS1 Suppresses Colorectal Carcinoma Aggressiveness by Inhibiting SATB2-Dependent Snail Transcription and Epithelial–Mesenchymal Transition
Authors: Wang Yi-Qing , Jiang Dong-Mei , Hu Sha-Sha , Zhao Li , Wang Lan , Yang Min-Hui , Ai Mei-Ling , Jiang Hui-Juan , Han Yue , Ding Yan-Qing , Wang Shuang
Published: March 2023

Supplementary Figures S1 through S11. (1) Supplementary Figure S1 shows the ectopical overexpressing of SATB2-AS1 in two CRC cell lines by lentivirus delivery. (2) Supplementary Figure S2 shows the effect of SATB2-AS1 on apoptosis in CRC cells. (3) Supplementary Figure S3 shows the effect of SATB2-AS1 knockdown mediated by siRNA on CRC cell proliferation, invasion and migration in vitro. (4) Supplementary Figure S4 shows the expression levels of SATB2 mRNA in CRC and adjacent non-cancerous tissues. (5) Supplementary Figure S5 shows the regulatory effect of SATB2-AS1 expression by SATB2. (6) Supplementary Figure S6 shows the effect of SATB2-AS1 on SATB2 mRNA stability. (7) Supplementary Figure S7 shows the enrichment amount of ZEB1-AS1 and PACER RNA with the p300 antibody by RIP assay. (8) Supplementary Figure S8 shows the regulatory effect of SATB2-AS1 on p300 mRNA. (9) Supplementary Figure S9 shows the inhibitory effects of SATB2-AS1 on M5 cells requiring p300 and SATB2. (10) Supplement Figure S10 shows the occupancy ability of p300 on Snail promoter by ChIP assay. (11) Supplementary Figure S11 shows the regulatory effect of Snail on SATB2-AS1 expression.
Supplementary Data from MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53
Authors: Hines John , Lartigue Schan , Dong Hanqing , Qian Yimin , Crews Craig M.
Published: March 2023

Figure S1 shows that treatment of cultured cells (HCT116) with the dual mode of action PROTAC A1874 results in an antiproliferative effect that is equally potent and more effective than a combination treatment with both component ligands (JQ1 and idasanutlin) at equivalent concentrations.
Figure S4 from A Gene Expression Classifier from Whole Blood Distinguishes Benign from Malignant Lung Nodules Detected by Low-Dose CT
Authors: Kossenkov Andrew V. , Qureshi Rehman , Dawany Noor B. , Wickramasinghe Jayamanna , Liu Qin , Majumdar R. Sonali , Chang Celia , Widura Sandy , Kumar Trisha , Horng Wen-Hwai , Konnisto Eric , Criner Gerard , Tsay Jun-Chieh J. , Pass Harvey , Yendamuri Sai , Vachani Anil , Bauer Thomas , Nam Brian , Rom William N. , Showe Michael K. , Showe Louise C.
Published: March 2023

Performance of NanoString Lung Nodule Classifier on training, testing and all sample set using different number of genes
Supplementary Data from SF3B2-Mediated RNA Splicing Drives Human Prostate Cancer Progression
Authors: Kawamura Norihiko , Nimura Keisuke , Saga Kotaro , Ishibashi Airi , Kitamura Koji , Nagano Hiromichi , Yoshikawa Yusuke , Ishida Kyoso , Nonomura Norio , Arisawa Mitsuhiro , Luo Jun , Kaneda Yasufumi
Published: March 2023

This file includes extended experimental procedures including 1. Cell culture and transfection, 2. Genome editing using CRISPR/Cas9 system, 3. Western blotting, 4. Production of Spliceostatin A, 5. PAR-CLIP,6. Bioinformatics and supplementary figure legends.
Supplementary Table S1 from Disruption of the Scaffolding Function of mLST8 Selectively Inhibits mTORC2 Assembly and Function and Suppresses mTORC2-Dependent Tumor Growth In Vivo
Authors: Hwang Yoonha , Kim Laura C. , Song Wenqiang , Edwards Deanna N. , Cook Rebecca S. , Chen Jin
Published: March 2023

Oligonucleotides used in study
Supplementary Methods from Sphingosine Kinase 1 Signaling Promotes Metastasis of Triple-Negative Breast Cancer
Authors: Acharya Sunil , Yao Jun , Li Ping , Zhang Chenyu , Lowery Frank J. , Zhang Qingling , Guo Hua , Qu Jingkun , Yang Fei , Wistuba Ignacio I. , Piwnica-Worms Helen , Sahin Aysegul A. , Yu Dihua
Published: March 2023

Plasmids construction; Cell proliferation assay; Migration assay and invasion assay; Transient transfection and luciferase reporter assay; Flow cytometry; Animal experiments; Case Selection, Tissue Microarray (TMA) Construction and analysis
Supplementary Figure 2 from Activation of Peroxisome Proliferator-Activated Receptors α and δ Synergizes with Inflammatory Signals to Enhance Adoptive Cell Therapy
Authors: Saibil Samuel D. , St. Paul Michael , Laister Robert C. , Garcia-Batres Carlos R. , Israni-Winger Kavita , Elford Alisha R. , Grimshaw Natasha , Robert-Tissot Céline , Roy Dominic G. , Jones Russell G. , Nguyen Linh T. , Ohashi Pamela S.
Published: March 2023

Glycolytic rate assay and ROS staining
Supplementary Figure S1 from A Model System for Studying the DNMT3A Hotspot Mutation (DNMT3AR882) Demonstrates a Causal Relationship between Its Dominant-Negative Effect and Leukemogenesis
Authors: Lu Rui , Wang Jun , Ren Zhihong , Yin Jiekai , Wang Yinsheng , Cai Ling , Wang Gang Greg
Published: March 2023

This contains Supplementary Figure S1, which shows transformation of TF1 cells by R882-mutated DNMT3A.
Supplementary Figure S1 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits
Authors: Corso Simona , Isella Claudio , Bellomo Sara E. , Apicella Maria , Durando Stefania , Migliore Cristina , Ughetto Stefano , D’Errico Laura , Menegon Silvia , Moya-Rull Daniel , Cargnelutti Marilisa , Capelôa Tânia , Conticelli Daniela , Giordano Jessica , Venesio Tiziana , Balsamo Antonella , Marchiò Caterina , Degiuli Maurizio , Reddavid Rossella , Fumagalli Uberto , De Pascale Stefano , Sgroi Giovanni , Rausa Emanuele , Baiocchi Gian Luca , Molfino Sarah , Pietrantonio Filippo , Morano Federica , Siena Salvatore , Sartore-Bianchi Andrea , Bencivenga Maria , Mengardo Valentina , Rosati Riccardo , Marrelli Daniele , Morgagni Paolo , Rausei Stefano , Pallabazzer Giovanni , De Simone Michele , Ribero Dario , Marsoni Silvia , Sottile Antonino , Medico Enzo , Cassoni Paola , Sapino Anna , Pectasides Eirini , Thorner Aaron R. , Nag Anwesha , Drinan Samantha D. , Wollison Bruce M. , Bass Adam J. , Giordano Silvia
Published: March 2023

Microsatellite instability (MSI) phenotype in primary gastric tumours and their corresponding PDX/ organoid
Supplementary Data from Enhancer Domains in Gastrointestinal Stromal Tumor Regulate KIT Expression and Are Targetable by BET Bromodomain Inhibition
Authors: Hemming Matthew L. , Lawlor Matthew A. , Andersen Jessica L. , Hagan Timothy , Chipashvili Otari , Scott Thomas G. , Raut Chandrajit P. , Sicinska Ewa , Armstrong Scott A. , Demetri George D. , Bradner James E.
Published: March 2023

Figure S1. Evaluation of the KIT locus in GIST cell lines. Figure S2. Effect of imatinib and JQ1 treatment on cell cycle and apoptosis in GIST cell lines. Figure S3. Effect of JQ1 and imatinib on KIT mRNA, protein and signaling. Figure S4. KIT rescue with enhancer independence in GIST430 and effects of HAND1 overexpression on KIT levels and drug sensitivity. Figure S5. Differences in GIST cell line enhancers and effects of drug treatment at the KIT locus in GIST430. Figure S6. H3K27ac ChIP-seq signal and RNA expression changes of exemplary genes following imatinib and/or JQ1 treatment in GIST. Figure S7. Expression and dependency of genes at the KIT locus in GIST cells. Figure S8. Combinatorial effects of bromodomain and KIT inhibition. Figure S9. Consequences of bromodomain inhibition in GIST xenograft models. Table S1. Oligonucleotide Sequences. Table S2. IC50 values in GIST cell lines.
Supplementary Table 1 from Heparanase Accelerates Obesity-Associated Breast Cancer Progression
Authors: Hermano Esther , Goldberg Rachel , Rubinstein Ariel M. , Sonnenblick Amir , Maly Bella , Nahmias Daniela , Li Jin-Ping , Bakker Marinka A.H. , van der Vlag Johan , Vlodavsky Israel , Peretz Tamar , Elkin Michael
Published: March 2023

Clinical and pathological characteristics of the study population
Supplementary Figure S1 from YAP1 Mediates Resistance to MEK1/2 Inhibition in Neuroblastomas with Hyperactivated RAS Signaling
Authors: Coggins Grace E. , Farrel Alvin , Rathi Komal S. , Hayes Colin M. , Scolaro Laura , Rokita Jo Lynne , Maris John M.
Published: March 2023

Figure S1A shows the two CRISPR gRNA targets. Figure S1B-E shows YAP1 knockout pools in neuroblastoma cell lines are sensitized to trametinib.
Supplementary Table 14 from Nod1 Imprints Inflammatory and Carcinogenic Responses toward the Gastric Pathogen Helicobacter pylori
Authors: Suarez Giovanni , Romero-Gallo Judith , Piazuelo Maria B. , Sierra Johanna C. , Delgado Alberto G. , Washington M. Kay , Shah Shailja C. , Wilson Keith T. , Peek Richard M.
Published: March 2023

Primer sequences used for real time RT-PCR quantification.
Supplementary Figure 1 from MDH1 and MPP7 Regulate Autophagy in Pancreatic Ductal Adenocarcinoma
Authors: New Maria , Van Acker Tim , Sakamaki Jun-Ichi , Jiang Ming , Saunders Rebecca E. , Long Jaclyn , Wang Victoria M.-Y. , Behrens Axel , Cerveira Joana , Sudhakar Padhmanand , Korcsmaros Tamas , Jefferies Harold B.J. , Ryan Kevin M. , Howell Michael , Tooze Sharon A.
Published: March 2023

Identification of autophagy-dependent and independent cell lines
Supplementary Data from RUNX1 Is a Driver of Renal Cell Carcinoma Correlating with Clinical Outcome
Authors: Rooney Nicholas , Mason Susan M. , McDonald Laura , Däbritz J. Henry M. , Campbell Kirsteen J. , Hedley Ann , Howard Steven , Athineos Dimitris , Nixon Colin , Clark William , Leach Joshua D.G. , Sansom Owen J. , Edwards Joanne , Cameron Ewan R. , Blyth Karen
Published: March 2023

All Supplementary data figures and legends. Supplementary Figure 1. In Silico analysis of RUNX1 expression in human kidney cancer. Supplementary Figure 2. Knockdown of RUNX1 with shRNA causes a growth defect in two ccRCC cell lines. Supplementary Figure 3. RUNX1 deletion in 786-O* cells and orthotopic xenograft. Supplementary Figure 4. Principle component analysis. Gene expression variances between control (786-O pX, Red) and RUNX1 CRISPR cells (786-O A1, yellow and 786-O A3, purple). Supplementary Figure 5. Heterozygous deletion of RUNX2 in a GEM model of kidney cancer does not affect survival.
Supplementary Material S3 from A Tumor-in-Host DEB-Based Approach for Modeling Cachexia and Bevacizumab Resistance
Authors: Tosca Elena M. , Rocchetti Maurizio , Pesenti Enrico , Magni Paolo
Published: March 2023

Growth chart and host-related model parameters
Supplementary Figure S1 from Activation of Canonical BMP4-SMAD7 Signaling Suppresses Breast Cancer Metastasis
Authors: Eckhardt Bedrich L. , Cao Yuan , Redfern Andrew D. , Chi Lap Hing , Burrows Allan D. , Roslan Suraya , Sloan Erica K. , Parker Belinda S. , Loi Sherene , Ueno Naoto T. , Lau Peter K. H. , Latham Bruce , Anderson Robin L.
Published: March 2023

Figure S1 shows the association of BMP4 expression with tumour aggressiveness and with metastasis-free survival
Supplementary Information from A Pygopus 2-Histone Interaction Is Critical for Cancer Cell Dedifferentiation and Progression in Malignant Breast Cancer
Authors: Saxena Meera , Kalathur Ravi K.R. , Rubinstein Natalia , Vettiger Andrea , Sugiyama Nami , Neutzner Melanie , Coto-Llerena Mairene , Kancherla Venkatesh , Ercan Caner , Piscuoglio Salvatore , Fischer Jonas , Fagiani Ernesta , Cantù Claudio , Basler Konrad , Christofori Gerhard
Published: March 2023

Supplementary Information containing 7 Suppl. Figures plus their legends, Suppl. Methods, Suppl. Table I and Suppl. References.
Supplementary Table 3 from Truncated ASPP2 Drives Initiation and Progression of Invasive Lobular Carcinoma via Distinct Mechanisms
Authors: Schipper Koen , Drenth Anne Paulien , van der Burg Eline , Cornelissen Samuel , Klarenbeek Sjoerd , Nethe Micha , Jonkers Jos
Published: March 2023

Criteria for histopathological classification of tumors
Suppl. Video 4 from A Pygopus 2-Histone Interaction Is Critical for Cancer Cell Dedifferentiation and Progression in Malignant Breast Cancer
Authors: Saxena Meera , Kalathur Ravi K.R. , Rubinstein Natalia , Vettiger Andrea , Sugiyama Nami , Neutzner Melanie , Coto-Llerena Mairene , Kancherla Venkatesh , Ercan Caner , Piscuoglio Salvatore , Fischer Jonas , Fagiani Ernesta , Cantù Claudio , Basler Konrad , Christofori Gerhard
Published: March 2023

Suppl. Video 4: Confocal analysis of a Pygo2AE/AE tumor spheroid stained for Axin-2. (Related to Figure S2D).
Suppl. Video 2 from A Pygopus 2-Histone Interaction Is Critical for Cancer Cell Dedifferentiation and Progression in Malignant Breast Cancer
Authors: Saxena Meera , Kalathur Ravi K.R. , Rubinstein Natalia , Vettiger Andrea , Sugiyama Nami , Neutzner Melanie , Coto-Llerena Mairene , Kancherla Venkatesh , Ercan Caner , Piscuoglio Salvatore , Fischer Jonas , Fagiani Ernesta , Cantù Claudio , Basler Konrad , Christofori Gerhard
Published: March 2023

Suppl. Video 2: Confocal analysis of a Pygo2AE/AE tumor spheroid stained for b-catenin. (Related to Figure S2C).
Supplementary files from An LTR Retrotransposon-Derived Long Noncoding RNA lncMER52A Promotes Hepatocellular Carcinoma Progression by Binding p120-Catenin
Authors: Wu Yangjun , Zhao Yiming , Huan Lin , Zhao Jingjing , Zhou Yuqiang , Xu Linguo , Hu Zhixiang , Liu Yizhe , Chen Zhiao , Wang Lu , Huang Shenglin , He Xianghuo , Liang Linhui
Published: March 2023

Supplementary data-The Supplementary information includes: Figure S1. The genomic location, subcellular distribution, full length and coding potential of lncMER52A. Figure S2. The knockdown efficiency and specificity of lncMER52A siRNAs and Crispr-Cas9 mediated knockdown. The effects of lncMER52A on the migration, invasion and metastasis of HCC cells. Figure S3. The correlation of lncMER52A and p120-catenin in HCC tissues and paired normal livers. Figure S4. lncMER52A overexpression significantly inhibited the interaction between β-TrCP1 and p120-catenin. Figure S5. The effects of p120-catenin on the migration and invasion of HCC cells in vitro. Figure S6. H3K4me3 and H3K27ac levels at the promoter of lncMER52A in Huh7 and HepG2-C3A cells. Table S1. Primers for RACE assays. Table S2. Sequence of siRNAs and gRNAs. Table S3. Primers used in molecular cloning of vectors. Table S4. Primers used in the RNA pulldown assays. Table S5. Primers used in the northern blot assays. Table S6. Primers used in the qPCR experiments. Table S7. Primers used in the ChIP assays. Table S8. The correlation of lncMER52A expression with HCC. clinicopathological features.
Supplementary Figure 5 from CoA Synthase (COASY) Mediates Radiation Resistance via PI3K Signaling in Rectal Cancer
Authors: Ferrandon Sylvain , DeVecchio Jennifer , Duraes Leonardo , Chouhan Hanumant , Karagkounis Georgios , Davenport Jacqueline , Orloff Matthew , Liska David , Kalady Matthew F.
Published: March 2023

COASY-mediated radioresistance is independent of APC/β-catenin activation pathway.
Supplementary Data from Unshielding Multidrug Resistant Cancer through Selective Iron Depletion of P-Glycoprotein–Expressing Cells
Authors: Cserepes Mihály , Türk Dóra , Tóth Szilárd , Pape Veronika F.S. , Gaál Anikó , Gera Melinda , Szabó Judit E. , Kucsma Nóra , Várady György , Vértessy Beáta G. , Streli Christina , Szabó Pál T. , Tovari Jozsef , Szoboszlai Norbert , Szakács Gergely
Published: March 2023

Supplementary tables and figures, supplementary materials and methods
Supplementary Methods, Figures, Tables, References from Inhibiting Translation Elongation with SVC112 Suppresses Cancer Stem Cells and Inhibits Growth in Head and Neck Squamous Carcinoma
Authors: Keysar Stephen B. , Gomes Nathan , Miller Bettina , Jackson Brian C. , Le Phuong N. , Morton J. Jason , Reisinger Julie , Chimed Tugs-Saikhan , Gomez Karina E. , Nieto Cera , Frederick Barbara , Pronk Gijsbertus J. , Somerset Hilary L. , Tan Aik-Choon , Wang Xiao-Jing , Raben David , Su Tin Tin , Jimeno Antonio
Published: March 2023

SF1 is related to Fig. 1 and Fig. 2. SVC112 inhibits tumor cells growth and enhances the effects of radiation. SF2 is related to Fig. 3. SVC112 combined with radiation inhibits growth of HNSCC PDX tumors. SF3. Ribo-seq analysis of HNSCC cells treated with SVC112. SF4 is related to Fig. 5. SVC112 suppresses proteins related to proliferation and CSCs. SF5 is related to Fig. 5. Reversibility of SVC112 treatment effects. SF6 is related to Fig. 5. Analysis of SVC112 resistance. SF7 is related to Fig. 6. Effects of exogenous Sox2 expression of SVC112 treatment. ST1 is related to Fig 1. Radiation dose modifying effects by SVC112. ST2 is related to Fig 3. Characteristics of HNSCC PDX cases treated with radiation and SVC112. ST3 is related to Fig 3. Incidence of histopathology in SVC112 treated mice. ST4. Ribo-seq analysis (GSEA, Hallmark Pathways) of HNSCC cells treated with SVC112.
Western Blots from A Sox2:miR-486-5p Axis Regulates Survival of GBM Cells by Inhibiting Tumor Suppressor Networks
Authors: Lopez-Bertoni Hernando , Kotchetkov Ivan S. , Mihelson Nicole , Lal Bachchu , Rui Yuan , Ames Heather , Lugo-Fagundo Maria , Guerrero-Cazares Hugo , Quiñones-Hinojosa Alfredo , Green Jordan J. , Laterra John
Published: March 2023

File contains full blots used for immunoblotting analysis.
Supplementary Movie 1 from Twist1-Induced Epithelial Dissemination Requires Prkd1 Signaling
Authors: Georgess Dan , Padmanaban Veena , Sirka Orit Katarina , Coutinho Kester , Choi Alex , Frid Gabriela , Neumann Neil M. , Inoue Takanari , Ewald Andrew J.
Published: March 2023

Early inhibition of Prkd1 blocks epithelial invasion into ECM and loss of cell-cell adhesion.
Supplementary Figure S2 from Resolution of Spatial and Temporal Heterogeneity in Bevacizumab-Treated Breast Tumors by Eigenspectra Multispectral Optoacoustic Tomography
Authors: Liapis Evangelos , Klemm Uwe , Karlas Angelos , Reber Josefine , Ntziachristos Vasilis
Published: March 2023

Supplementary Figure S2
Supplementary Data from Targeting the PI3K/mTOR Pathway Augments CHK1 Inhibitor–Induced Replication Stress and Antitumor Activity in High-Grade Serous Ovarian Cancer
Authors: Huang Tzu-Ting , Brill Ethan , Nair Jayakumar R. , Zhang Xiaohu , Wilson Kelli M. , Chen Lu , Thomas Craig J. , Lee Jung-Min
Published: March 2023

Clean version of supplementary Data
Supplementary Data from Subcellular Distribution of p53 by the p53-Responsive lncRNA NBAT1 Determines Chemotherapeutic Response in Neuroblastoma
Authors: Mitra Sanhita , Muralidharan Somsundar Veppil , Di Marco Mirco , Juvvuna Prasanna Kumar , Kosalai Subazini Thankaswamy , Reischl Silke , Jachimowicz Daniel , Subhash Santhilal , Raimondi Ivan , Kurian Leo , Huarte Maite , Kogner Per , Fischer Matthias , Johnsen John Inge , Mondal Tanmoy , Kanduri Chandrasekhar
Published: March 2023

Supplementary Text, Supplementary Table Legends
Supplementary Table S1 from Integrated Genomic Characterization of the Human Immunome in Cancer
Authors: Li Yongsheng , Burgman Brandon , McGrail Daniel J. , Sun Ming , Qi Dan , Shukla Sachet A. , Wu Erxi , Capasso Anna , Lin Shiaw-Yih , Wu Catherine J. , Eckhardt S. Gail , Mills Gordon B. , Li Bo , Sahni Nidhi , Yi S. Stephen
Published: March 2023

Table S1. The GSEA score and p-values for differentially expressed genes that are immunologically relevant.
Figure S1 from Erbin Suppresses KSR1-Mediated RAS/RAF Signaling and Tumorigenesis in Colorectal Cancer
Authors: Stevens Payton D. , Wen Yang-An , Xiong Xiaopeng , Zaytseva Yekaterina Y. , Li Austin T. , Wang Chi , Stevens Ashley T. , Farmer Trevor N. , Gan Tong , Weiss Heidi L. , Inagaki Masaki , Marchetto Sylvie , Borg Jean-Paul , Gao Tianyan
Published: March 2023

Figure S1. Erbin is downregulated and mislocalized in CRC patient samples. (A) To determine the stage dependent expression of ERBIN in CRC patients, TCGA Colorectal Cancer dataset was used for the analyses. Five boxplots were created based upon the stage of cancer present (Normal, Stage I, Stage II, Stage III, and Stage IV). ANOVA tests were performed to determine if at least one of the stages differed significantly from the others. A Tukey Honest Significant Difference test (Tukey HSD) was then conducted to determine which pairs of stages differed significantly from each other. Results showed that the expression of ERBIN was significantly decreased in each stage of CRC patients compared with normal controls (p<0.0001 for each stage). However, there was no significant difference between any stages. (B) Representative images of IHC staining for Erbin in CRC TMA, which contains 45 pairs of marched normal and tumor tissues. Erbin was localized to the basolateral membranes in normal tissues and diffuse in tumor tissues. Scale bar, 100μm. (C) De-identified patient data associated with tissues used for detecting Erbin protein expression by western blot.
Supplementary Figures from The Pathognomonic FOXL2 C134W Mutation Alters DNA-Binding Specificity
Authors: Carles Annaïck , Trigo-Gonzalez Genny , Cao Qi , Cheng S.-W. Grace , Moksa Michelle , Bilenky Misha , Huntsman David G. , Morin Gregg B. , Hirst Martin
Published: March 2023

File containing supplemental figures and legends
Table S1 from Chromothripsis in Human Breast Cancer
Authors: Bolkestein Michiel , Wong John K.L. , Thewes Verena , Körber Verena , Hlevnjak Mario , Elgaafary Shaymaa , Schulze Markus , Kommoss Felix K.F. , Sinn Hans-Peter , Anzeneder Tobias , Hirsch Steffen , Devens Frauke , Schröter Petra , Höfer Thomas , Schneeweiss Andreas , Lichter Peter , Zapatka Marc , Ernst Aurélie
Published: March 2023

Description of the patient cohorts and available data
Supplementary Table from A Hyperactive RelA/p65-Hexokinase 2 Signaling Axis Drives Primary Central Nervous System Lymphoma
Authors: Tateishi Kensuke , Miyake Yohei , Kawazu Masahito , Sasaki Nobuyoshi , Nakamura Taishi , Sasame Jo , Yoshii Yukie , Ueno Toshihide , Miyake Akio , Watanabe Jun , Matsushita Yuko , Shiba Norio , Udaka Naoko , Ohki Kentaro , Fink Alexandria L. , Tummala Shilpa S. , Natsumeda Manabu , Ikegaya Naoki , Nishi Mayuko , Ohtake Makoto , Miyazaki Ryohei , Suenaga Jun , Murata Hidetoshi , Aoki Ichio , Miller Julie J. , Fujii Yukihiko , Ryo Akihide , Yamanaka Shoji , Mano Hiroyuki , Cahill Daniel P. , Wakimoto Hiroaki , Chi Andrew S. , Batchelor Tracy T. , Nagane Motoo , Ichimura Koichi , Yamamoto Tetsuya
Published: March 2023

Supplementary Table S1-S12
Supplementary Data from Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer
Authors: Gupta Vineet K. , Sharma Nikita S. , Durden Brittany , Garrido Vanessa T. , Kesh Kousik , Edwards Dujon , Wang Dezhen , Myer Ciara , Mateo-Victoriano Beatriz , Kollala Sai Sundeep , Ban Yuguang , Gao Zhen , Bhattacharya Sanjoy K. , Saluja Ashok , Singh Pankaj K. , Banerjee Sulagna
Published: March 2023

Supplementary Figures and methods
Table S1 from Macrophage-Derived Cholesterol Contributes to Therapeutic Resistance in Prostate Cancer
Authors: El-Kenawi Asmaa , Dominguez-Viqueira William , Liu Min , Awasthi Shivanshu , Abraham-Miranda Julieta , Keske Aysenur , Steiner KayLee K. , Noel Leenil , Serna Amparo N. , Dhillon Jasreman , Gillies Robert J. , Yu Xiaoqing , Koomen John M. , Yamoah Kosj , Gatenby Robert A. , Ruffell Brian
Published: March 2023

Key resources
Figure S5 from Macrophage-Derived Cholesterol Contributes to Therapeutic Resistance in Prostate Cancer
Authors: El-Kenawi Asmaa , Dominguez-Viqueira William , Liu Min , Awasthi Shivanshu , Abraham-Miranda Julieta , Keske Aysenur , Steiner KayLee K. , Noel Leenil , Serna Amparo N. , Dhillon Jasreman , Gillies Robert J. , Yu Xiaoqing , Koomen John M. , Yamoah Kosj , Gatenby Robert A. , Ruffell Brian
Published: March 2023

Effect of LXR agonist and antagonist on prostate cancer gene expression and LDL uptake
Supplementary Table 3 from A lncRNA TCL6-miR-155 Interaction Regulates the Src-Akt-EMT Network to Mediate Kidney Cancer Progression and Metastasis
Authors: Kulkarni Priyanka , Dasgupta Pritha , Hashimoto Yutaka , Shiina Marisa , Shahryari Varahram , Tabatabai Z. Laura , Yamamura Soichiro , Tanaka Yuichiro , Saini Sharanjot , Dahiya Rajvir , Majid Shahana
Published: March 2023

Clinicopathological features
Supplementary Table 3 from CKAP2L Promotes Non–Small Cell Lung Cancer Progression through Regulation of Transcription Elongation
Authors: Monteverde Tiziana , Sahoo Sudhakar , La Montagna Manuela , Magee Peter , Shi Lei , Lee Dave , Sellers Robert , Baker Alexander R. , Leong Hui Sun , Fassan Matteo , Garofalo Michela
Published: March 2023

Functional annotation analysis of genes showing RPB1 reduced binding upon CKAP2L downregulation
Supplementary Data from Dual Covalent Inhibition of PKM and IMPDH Targets Metabolism in Cutaneous Metastatic Melanoma
Authors: Zerhouni Marwa , Martin Anthony R. , Furstoss Nathan , Gutierrez Vincent S. , Jaune Emilie , Tekaya Nedra , Beranger Guillaume E. , Abbe Patricia , Regazzetti Claire , Amdouni Hella , Driowya Mohsine , Dubreuil Patrice , Luciano Frédéric , Jacquel Arnaud , Tulic Meri K. , Cluzeau Thomas , O'Hara Brendan P. , Ben-Sahra Issam , Passeron Thierry , Benhida Rachid , Robert Guillaume , Auberger Patrick , Rocchi Stéphane
Published: March 2023

Western Blot quantification
Table S1 from Altering the Microbiome Inhibits Tumorigenesis in a Mouse Model of Oviductal High-Grade Serous Carcinoma
Authors: Chen Lixing , Zhai Yali , Wang Yisheng , Fearon Eric R. , Núñez Gabriel , Inohara Naohiro , Cho Kathleen R.
Published: March 2023

PCR primer sequences
Supplementary Information from Host-Dependent Phenotypic Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Haga Yuya , Marrocco Ilaria , Noronha Ashish , Uribe Mary Luz , Nataraj Nishanth Belugali , Sekar Arunachalam , Drago-Garcia Diana , Borgoni Simone , Lindzen Moshit , Giri Suvendu , Wiemann Stefan , Tsutsumi Yasuo , Yarden Yosef
Published: March 2023

Supplementary Materials and Methods
Supplementary Data from Locus-Specific Characterization of Human Endogenous Retrovirus Expression in Prostate, Breast, and Colon Cancers
Authors: Steiner Margaret C. , Marston Jez L. , Iñiguez Luis P. , Bendall Matthew L. , Chiappinelli Katherine B. , Nixon Douglas F. , Crandall Keith A.
Published: March 2023

Supplemental tables and figures as referenced in the manuscript.
Supplementary Figure S6 from The Common Germline TP53-R337H Mutation Is Hypomorphic and Confers Incomplete Penetrance and Late Tumor Onset in a Mouse Model
Authors: Jeffers John R. , Pinto Emilia M. , Rehg Jerold E. , Clay Michael R. , Wang Jinling , Neale Geoffrey , Heath Richard J. , Lozano Guillermina , Lalli Enzo , Figueiredo Bonald C. , Pappo Alberto S. , Rodriguez-Galindo Carlos , Chen Wenan , Pounds Stanley , Ribeiro Raul C. , Zambetti Gerard P.
Published: March 2023

Senescence associated β-galactosidase expression and ROS levels in mutant p53-R334H primary MEFs.
Supplementary Figure S4 from The Common Germline TP53-R337H Mutation Is Hypomorphic and Confers Incomplete Penetrance and Late Tumor Onset in a Mouse Model
Authors: Jeffers John R. , Pinto Emilia M. , Rehg Jerold E. , Clay Michael R. , Wang Jinling , Neale Geoffrey , Heath Richard J. , Lozano Guillermina , Lalli Enzo , Figueiredo Bonald C. , Pappo Alberto S. , Rodriguez-Galindo Carlos , Chen Wenan , Pounds Stanley , Ribeiro Raul C. , Zambetti Gerard P.
Published: March 2023

Strong nuclear staining of mutant TP53-R337H protein in normal tissue of carriers who developed ACC.
Supplement Figure 3 from Targeting an Inducible SALL4-Mediated Cancer Vulnerability with Sequential Therapy
Authors: Yang Junyu , Gao Chong , Liu Miao , Liu Yao-Chung , Kwon Junsu , Qi Jun , Tian Xi , Stein Alicia , Liu Yanjing V. , Kong Nikki R. , Wu Yue , Yin Shenyi , Xi Jianzhong , Chen Zhiyuan , Kumari Kalpana , Wong Hannan , Luo Hongbo , Silberstein Leslie E. , Thoms Julie A.I. , Unnikrishnan Ashwin , Pimanda John E. , Tenen Daniel G. , Chai Li
Published: March 2023

Supplement Figure 3
Supplementary Data from The Common Germline TP53-R337H Mutation Is Hypomorphic and Confers Incomplete Penetrance and Late Tumor Onset in a Mouse Model
Authors: Jeffers John R. , Pinto Emilia M. , Rehg Jerold E. , Clay Michael R. , Wang Jinling , Neale Geoffrey , Heath Richard J. , Lozano Guillermina , Lalli Enzo , Figueiredo Bonald C. , Pappo Alberto S. , Rodriguez-Galindo Carlos , Chen Wenan , Pounds Stanley , Ribeiro Raul C. , Zambetti Gerard P.
Published: March 2023

Supplemental Materials and Methods and Supplementary Figure Legends
Supplementary Methods from Recruitment of KMT2C/MLL3 to DNA Damage Sites Mediates DNA Damage Responses and Regulates PARP Inhibitor Sensitivity in Cancer
Authors: Chang Antao , Liu Liang , Ashby Justin M. , Wu Dan , Chen Yanan , O'Neill Stacey S. , Huang Shan , Wang Juan , Wang Guanwen , Cheng Dongmei , Tan Xiaoming , Petty W.J. , Pasche Boris C. , Xiang Rong , Zhang Wei , Sun Peiqing
Published: March 2023

Supplementary Methods
Table S2 from Chr20q Amplification Defines a Distinct Molecular Subtype of Microsatellite Stable Colorectal Cancer
Authors: Zhang Baoyi , Yao Kevin , Zhou Emily , Zhang Lanjing , Cheng Chao
Published: March 2023

Table S2. Chr20q amplification status of 22 selected MSS cell lines. The Chr20q amplification status is listed in second column with 1 and 0 represent amplification and non-amplification respectively.
Supplementary Information from Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers
Authors: Namba Shinichi , Saito Yuki , Kogure Yasunori , Masuda Tatsuo , Bondy Melissa L. , Gharahkhani Puya , Gockel Ines , Heider Dominik , Hillmer Axel , Jankowski Janusz , MacGregor Stuart , Maj Carlo , Melin Beatrice , Ostrom Quinn T. , Palles Claire , Schumacher Johannes , Tomlinson Ian , Whiteman David C. , Okada Yukinori , Kataoka Keisuke
Published: March 2023

Figures S1–S11, Tables S1–S6, Supplementary Materials and Methods, Supplementary Notes, and Supplementary References
Supporting Figures from A Pro-Regenerative Environment Triggers Premalignant to Malignant Transformation of Senescent Hepatocytes
Authors: Wuestefeld Anna , Iakovleva Viktoriia , Yap Shirlyn Xue Ling , Ong Agnes Bee Leng , Huang Daniel Q. , Shuen Timothy Wai Ho , Toh Han Chong , Dan Yock Young , Zender Lars , Wuestefeld Torsten
Published: March 2023

Supporting Figures and Figure legends
Supplementary Figure 2 from KDM6A Loss Triggers an Epigenetic Switch That Disrupts Urothelial Differentiation and Drives Cell Proliferation in Bladder Cancer
Authors: Qiu Hong , Makarov Vladimir , Bolzenius Jennifer K. , Halstead Angela , Parker Yvonne , Wang Allen , Iyer Gopakumar V. , Wise Hannah , Kim Daniel , Thayaparan Varna , Lindner Daniel J. , Haber Georges-Pascal , Ting Angela H. , Ren Bing , Chan Timothy A. , Arora Vivek , Solit David B. , Lee Byron H.
Published: March 2023

Supplementary Figure 2
Table S3 from Systematic Interrogation of Tumor Cell Resistance to Chimeric Antigen Receptor T-cell Therapy in Pancreatic Cancer
Authors: Hagel Kimberly R. , Arafeh Rand , Gang Sydney , Arnoff Taylor E. , Larson Rebecca C. , Doench John G. , Mathewson Nathan D. , Wucherpfennig Kai W. , Maus Marcela V. , Hahn William C.
Published: March 2023

expression of Hallmark IFNγ/IFNα gene sets in HupT3 cells following TFAP4 knockout and overexpression
Supplementary Data from Systematic Interrogation of Tumor Cell Resistance to Chimeric Antigen Receptor T-cell Therapy in Pancreatic Cancer
Authors: Hagel Kimberly R. , Arafeh Rand , Gang Sydney , Arnoff Taylor E. , Larson Rebecca C. , Doench John G. , Mathewson Nathan D. , Wucherpfennig Kai W. , Maus Marcela V. , Hahn William C.
Published: March 2023

Supplemental figures 1-6
Data from Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors
Authors: Yi Joo Mi , Tsai Hsing-Chen , Glöckner Sabine C. , Lin Steven , Ohm Joyce E. , Easwaran Hari , James C. David , Costello Joseph F. , Riggins Gregory , Eberhart Charles G. , Laterra John , Vescovi Angelo L. , Ahuja Nita , Herman James G. , Schuebel Kornel E. , Baylin Stephen B.
Published: March 2023

Abstract
Much recent effort has focused on identifying and characterizing cellular markers that distinguish tumor propagating cells (TPC) from more differentiated progeny. We report here an unusual promoter DNA methylation pattern for one such marker, the cell surface antigen CD133 (Prominin 1). This protein has been extensively used to enrich putative cancer propagating stem-like cell populations in epithelial tumors and, especially, glioblastomas. We find that, within individual cell lines of cultured colon cancers and glioblastomas, the promoter CpG island of CD133 is DNA methylated, primarily, in cells with absent or low expression of the marker protein, whereas lack of such methylation is evident in purely CD133+ cells. Differential histone modification marks of active versus repressed genes accompany these DNA methylation changes. This heterogeneous CpG island DNA methylation status in the tumors is unusual in that other DNA hypermethylated genes tested in such cultures preserve their methylation patterns between separated CD133+ and CD133− cell populations. Furthermore, the CD133 DNA methylation seems to constitute an abnormal promoter signature because it is not found in normal brain and colon but only in cultured and primary tumors. Thus, the DNA methylation is imposed on the transition between the active versus repressed transcription state for CD133 only in tumors. Our findings provide additional insight for the dynamics of aberrant DNA methylation associated with aberrant gene silencing in human tumors. [Cancer Res 2008;68(19):8094–103]
Data from Cells Silenced for SDHB Expression Display Characteristic Features of the Tumor Phenotype
Authors: Cervera Ana M. , Apostolova Nadezda , Crespo Francisco Luna , Mata Manuel , McCreath Kenneth J.
Published: March 2023

Abstract
Recently, enzymes of the tricarboxylic acid (TCA) cycle have emerged as novel tumor suppressors. In particular, mutations in the nuclear-encoded subunits of succinate dehydrogenase (SDHB, SDHC, and SDHD) cause paragangliomas and pheochromocytomas. Although the mechanism(s) by which disruption of mitochondrial metabolism leads to neoplasia is largely unknown, increasing evidence points to an activation of pseudohypoxia. In this study, we have shown that silencing of SDHB using DNA-based small interfering RNA resulted in major impairments in cellular proliferation, respiration, and a corresponding shift to glycolysis. The levels of reactive oxygen species, however, were unchanged. As expected, hypoxia-inducible factor-1α (HIF-1α) and HIF-2α were up-regulated in chronically silenced cells, suggesting that a pseudohypoxic state was attained. In addition, the c-Jun amino-terminal kinase and p38 kinase stress signaling proteins were hyperphosphorylated in SDHB-silenced cells. Microarray analysis showed that >400 genes were influenced (6-fold or more up-regulation or down-regulation) by silencing of SDHB, confirming the importance of the TCA cycle in cellular metabolism. Examples of dysregulated genes included those involved in proliferation, adhesion, and the hypoxia pathway. Of interest, SDHB-silenced cells had a greater capacity to adhere to extracellular matrix components, including fibronectin and laminin, than control cells, thus suggesting a possible mechanism of tumor initiation. Although transient silencing of the HIF-1α transcription factor in SDHB-silenced cells had little effect on the expression of a subset of up-regulated genes, it partially reversed the adhesion phenotype to fibronectin, pointing to a potentially important role for HIF-1 in this process. [Cancer Res 2008;68(11):4058–67]
Data from Tumor Regression in Mice by Delivery of Bcl-2 Small Interfering RNA with Pegylated Cationic Liposomes
Authors: Sonoke Satoru , Ueda Toshihiro , Fujiwara Kae , Sato Yohei , Takagaki Kazuchika , Hirabayashi Kazuko , Ohgi Tadaaki , Yano Junichi
Published: March 2023

Abstract
The pharmacokinetics and antitumor activity of pegylated small interfering RNA (siRNA)/cationic liposome complexes were studied after systemic administration to mice. We designed pegylated-lipid carriers for achieving increased plasma concentrations of RNA and hence improved accumulation of RNA in tumors by the enhanced permeability and retention effect. We compared the pharmacokinetics of siRNA complexed with liposomes incorporating pegylated lipids with longer (C-17 or C-18), shorter (C-12 to C-16), or unsaturated (C-18:1) acyl chains. When longer acyl chains were used, the plasma concentrations of siRNA obtained were dramatically higher than when shorter or unsaturated chains were used. This may be explained by the higher gel-to-liquid-crystalline phase-transition temperature (Tc) of lipids with longer acyl chains, which may form more rigid liposomes with reduced uptake by the liver. We tested a siRNA that is sequence specific for the antiapoptotic bcl-2 mRNA complexed with a pegylated liposome incorporating a C-18 lipid (PEG-LIC) by i.v. administration in a mouse model of human prostate cancer. Three-fold higher accumulation of RNA in the tumors was achieved when PEG-LIC rather than nonpegylated liposomes was used, and sequence-specific antitumor activity was observed. Our siRNA/PEG-LIC complex showed no side effects on repeated administration and the strength of its antitumor activity may be attributed to its high uptake by the tumors. Pegylation of liposomes improved the plasma retention, uptake by s.c. tumors, and antitumor activity of the encapsulated siRNA. PEG-LIC is a promising candidate for siRNA cancer therapy. [Cancer Res 2008;68(21):8843–51]
Data from Prostaglandin E2 Regulates Tumor Angiogenesis in Prostate Cancer
Authors: Jain Shalini , Chakraborty Goutam , Raja Remya , Kale Smita , Kundu Gopal C.
Published: March 2023

Abstract
In cancer management, the cyclooxygenase (COX)–targeted approach has shown great promise in anticancer therapeutics. However, the use of COX-2 inhibitors has side effects and health hazards; thus, targeting its major metabolite prostaglandin E2 (PGE2)–mediated signaling pathway might be a rational approach for the next generation of cancer management. Recent studies on several in vitro and in vivo models have revealed that elevated expression of COX-2 correlates with prostate tumor growth and angiogenesis. In this study, we have shown the in-depth molecular mechanism and the PGE2 activation of the epidermal growth factor receptor and β3 integrin through E prostanoid 2 (EP2)–mediated and EP4-mediated pathways, which lead to activator protein-1 (AP-1) activation. Moreover, PGE2 also induces activating transcription factor-4 (ATF-4) activation and stimulates cross-talk between ATF-4 and AP-1, which is unidirectional toward AP-1, which leads to the increased expressions of urokinase-type plasminogen activator and vascular endothelial growth factor and, eventually, regulates prostate tumor cell motility. In vivo Matrigel angiogenesis assay data revealed that PGE2 induces angiogenesis through EP2 and EP4. Human prostate cancer specimen analysis also supported our in vitro and in vivo studies. Our data suggest that targeting PGE2 signaling pathway (i.e., blocking EP2 and EP4 receptors) might be a rational therapeutic approach for overcoming the side effects of COX-2 inhibitors and that this might be a novel strategy for the next generation of prostate cancer management. [Cancer Res 2008;68(19):7750–9]
Data from Translation Inhibitor Pdcd4 Is Targeted for Degradation during Tumor Promotion
Authors: Schmid Tobias , Jansen Aaron P. , Baker Alyson R. , Hegamyer Glenn , Hagan John P. , Colburn Nancy H.
Published: March 2023

Abstract
Inactivation of tumor suppressors is among the rate-limiting steps in carcinogenesis that occur during the tumor promotion stage. The translation inhibitor programmed cell death 4 (Pdcd4) suppresses tumorigenesis and invasion. Although Pdcd4 is not mutationally inactivated in human cancer, the mechanisms controlling Pdcd4 inactivation during tumorigenesis remain elusive. We report that tumor promoter 12-O-tetradecanoylphorbol-13-acetate exposure decreases protein levels of Pdcd4 in mouse skin papillomas and keratinocytes as well as in human HEK293 cells. This decrease is attributable to increased proteasomal degradation of Pdcd4 and is mediated by protein kinase C–dependent activation of phosphatidylinositol 3-kinase–Akt–mammalian target of rapamycin–p70S6K and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)–ERK signaling. Both Akt and p70S6K phosphorylate Pdcd4, allowing for binding of the E3-ubiquitin ligase β-TrCP and consequently ubiquitylation. MEK-ERK signaling on the other hand facilitates the subsequent proteasomal degradation. We further show that Pdcd4 protein levels in vivo are limiting for tumor formation, establishing Pdcd4 as a haploinsufficient tumor suppressor in Pdcd4-deficient mice. Thus, because endogenous Pdcd4 levels are limiting for tumorigenesis, inhibiting signaling to Pdcd4 degradation may prove a valid strategy for cancer prevention and intervention. [Cancer Res 2008;68(5):1254–60]
Data from Reconstitution of Nasopharyngeal Carcinoma–Type EBV Infection Induces Tumorigenicity
Authors: Seto Eri , Ooka Tadamasa , Middeldorp Jaap , Takada Kenzo
Published: March 2023

Abstract
Several reports have shown that the EBV-encoded BARF1 gene has oncogenic activity. We have recently reported that BARF1 is expressed as a latent gene in most nasopharyngeal carcinomas (NPC), suggesting that BARF1 may have an important role in NPC oncogenesis. However, we found that when the NPC-derived EBV-negative cell lines, HONE-1 and CNE-1, were infected with EBV in vitro, BARF1 was not expressed, although the expression of other latent genes was identical to that of NPC tumors. Therefore, we generated a recombinant EBV (rEBV) carrying the BARF1 gene (BARF1-rEBV) under the SV40 promoter to reconstitute the NPC-type EBV infection. NPC-derived EBV-negative cell lines were stably infected with either a wild-type rEBV (wild-rEBV) or BARF1-rEBV. The resultant BARF1-rEBV–infected NPC cell clones represented NPC-type EBV expression, and BARF1 expression was similar to that observed in NPC tissues. BARF1-rEBV–infected cell clones grew to a higher cell density and were more resistant to apoptosis than wild-rEBV–infected counterparts. BARF1 protein was quickly secreted into the culture medium, and secreted BARF1 contributed to the increase of cell densities in NPC cells, but it had no effect on resistance to apoptosis. Furthermore, BARF1-rEBV–infected cell clones became tumorigenic in nude mice. These results suggest that BARF1 plays an important role in NPC development. [Cancer Res 2008;68(4):1030–6]