bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Table 2 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules
Authors: Singh Kamini , Lin Jianan , Lecomte Nicolas , Mohan Prathibha , Gokce Askan , Sanghvi Viraj R. , Jiang Man , Grbovic-Huezo Olivera , Burčul Antonija , Stark Stefan G. , Romesser Paul B. , Chang Qing , Melchor Jerry P. , Beyer Rachel K. , Duggan Mark , Fukase Yoshiyuki , Yang Guangli , Ouerfelli Ouathek , Viale Agnes , de Stanchina Elisa , Stamford Andrew W. , Meinke Peter T. , Rätsch Gunnar , Leach Steven D. , Ouyang Zhengqing , Wendel Hans-Guido
Published: March 2023

Supplementary Table 2
Supplementary Legends from A Fusion Transcription Factor–Driven Cancer Progresses to a Fusion-Independent Relapse via Constitutive Activation of a Downstream Transcriptional Target
Authors: Boudjadi Salah , Pandey Puspa Raj , Chatterjee Bishwanath , Nguyen Thanh Hung , Sun Wenyue , Barr Frederic G.
Published: March 2023

The File includes the legends of the supplementary figures and supplementary table 1
Supplementary Table 1 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules
Authors: Singh Kamini , Lin Jianan , Lecomte Nicolas , Mohan Prathibha , Gokce Askan , Sanghvi Viraj R. , Jiang Man , Grbovic-Huezo Olivera , Burčul Antonija , Stark Stefan G. , Romesser Paul B. , Chang Qing , Melchor Jerry P. , Beyer Rachel K. , Duggan Mark , Fukase Yoshiyuki , Yang Guangli , Ouerfelli Ouathek , Viale Agnes , de Stanchina Elisa , Stamford Andrew W. , Meinke Peter T. , Rätsch Gunnar , Leach Steven D. , Ouyang Zhengqing , Wendel Hans-Guido
Published: March 2023

Supplementary Table 1
Supplementary Figure S1 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules
Authors: Singh Kamini , Lin Jianan , Lecomte Nicolas , Mohan Prathibha , Gokce Askan , Sanghvi Viraj R. , Jiang Man , Grbovic-Huezo Olivera , Burčul Antonija , Stark Stefan G. , Romesser Paul B. , Chang Qing , Melchor Jerry P. , Beyer Rachel K. , Duggan Mark , Fukase Yoshiyuki , Yang Guangli , Ouerfelli Ouathek , Viale Agnes , de Stanchina Elisa , Stamford Andrew W. , Meinke Peter T. , Rätsch Gunnar , Leach Steven D. , Ouyang Zhengqing , Wendel Hans-Guido
Published: March 2023

Supplementary Figure S1
Figure S4 from Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy
Authors: Sandoval-Acuña Cristian , Torrealba Natalia , Tomkova Veronika , Jadhav Sukanya B. , Blazkova Kristyna , Merta Ladislav , Lettlova Sandra , Adamcová Miroslava K. , Rosel Daniel , Brábek Jan , Neuzil Jiri , Stursa Jan , Werner Lukas , Truksa Jaroslav
Published: March 2023

High Resolution Supplementary Figure S4
Figure S2 from Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy
Authors: Sandoval-Acuña Cristian , Torrealba Natalia , Tomkova Veronika , Jadhav Sukanya B. , Blazkova Kristyna , Merta Ladislav , Lettlova Sandra , Adamcová Miroslava K. , Rosel Daniel , Brábek Jan , Neuzil Jiri , Stursa Jan , Werner Lukas , Truksa Jaroslav
Published: March 2023

High Resolution Supplementary Figure 2
Supplementary Data from Functional Analysis of MET Exon 14 Skipping Alteration in Cancer Invasion and Metastatic Dissemination
Authors: Wang Feng , Liu Yang , Qiu Wanglong , Shum Elaine , Feng Monica , Zhao Dejian , Zheng Deyou , Borczuk Alain , Cheng Haiying , Halmos Balazs
Published: March 2023

Supplementary Data from Functional Analysis of MET Exon 14 Skipping Alteration in Cancer Invasion and Metastatic Dissemination
Supplementary Data from Activation of YAP1 by N6-Methyladenosine–Modified circCPSF6 Drives Malignancy in Hepatocellular Carcinoma
Authors: Chen Yunhao , Ling Zhenan , Cai Xianlei , Xu Yongfang , Lv Zhen , Man Da , Ge Jiangzhen , Yu Chengkuan , Zhang Deguo , Zhang Yanpeng , Xie Haiyang , Zhou Lin , Wu Jian , Zheng Shusen
Published: March 2023

Supplementary Data from Activation of YAP1 by N6-Methyladenosine–Modified circCPSF6 Drives Malignancy in Hepatocellular Carcinoma
Supplementary Figure from Autocrine Canonical Wnt Signaling Primes Noncanonical Signaling through ROR1 in Metastatic Castration-Resistant Prostate Cancer
Authors: Ma Fen , Arai Seiji , Wang Keshan , Calagua Carla , Yuan Amanda R. , Poluben Larysa , Gu Zhongkai , Russo Joshua W. , Einstein David J. , Ye Huihui , He Meng Xiao , Liu Yu , Van Allen Eliezer , Sowalsky Adam G. , Bhasin Manoj K. , Yuan Xin , Balk Steven P.
Published: March 2023

Supplementary Figure from Autocrine Canonical Wnt Signaling Primes Noncanonical Signaling through ROR1 in Metastatic Castration-Resistant Prostate Cancer
Supplementary Table from Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma
Authors: O'Connor Caitlin M. , Taylor Sarah E. , Miller Kathryn M. , Hurst Lauren , Haanen Terrance J. , Suhan Tahra K. , Zawacki Kaitlin P. , Noto Fallon K. , Trako Jonida , Mohan Arathi , Sangodkar Jaya , Zamarin Dmitriy , DiFeo Analisa , Narla Goutham
Published: March 2023

Supplementary Table from Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma
Supplementary Data from Metabolic and Nonmetabolic Functions of PSAT1 Coordinate Signaling Cascades to Confer EGFR Inhibitor Resistance and Drive Progression in Lung Adenocarcinoma
Authors: Luo Ming-Yu , Zhou Ye , Gu Wei-Ming , Wang Cheng , Shen Ning-Xiang , Dong Jiang-Kai , Lei Hui-Min , Tang Ya-Bin , Liang Qian , Zou Jing-Hua , Xu Lu , Ma Pengfei , Zhuang Guanglei , Bi Ling , Xu Ling , Zhu Liang , Chen Hong-Zhuan , Shen Ying
Published: March 2023

Supplementary Data from Metabolic and Nonmetabolic Functions of PSAT1 Coordinate Signaling Cascades to Confer EGFR Inhibitor Resistance and Drive Progression in Lung Adenocarcinoma
Supplementary Data from An Active Learning Framework Improves Tumor Variant Interpretation
Authors: Blee Alexandra M. , Li Bian , Pecen Turner , Meiler Jens , Nagel Zachary D. , Capra John A. , Chazin Walter J.
Published: March 2023

Supplementary Data from An Active Learning Framework Improves Tumor Variant Interpretation
Supplementary Figure from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
Authors: O'Leary Patrick C. , Chen Huadong , Doruk Yagmur U. , Williamson Tess , Polacco Benjamin , McNeal Andrew S. , Shenoy Tanushree , Kale Nupura , Carnevale Julia , Stevenson Erica , Quigley David A. , Chou Jonathan , Feng Felix Y. , Swaney Danielle L. , Krogan Nevan J. , Kim Minkyu , Diolaiti Morgan E. , Ashworth Alan
Published: March 2023

Supplementary Figure from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
Supplementary Data from Cyclocreatine Suppresses Creatine Metabolism and Impairs Prostate Cancer Progression
Authors: Patel Rachana , Ford Catriona A. , Rodgers Lisa , Rushworth Linda K. , Fleming Janis , Mui Ernest , Zhang Tong , Watson David , Lynch Victoria , Mackay Gillian , Sumpton David , Sansom Owen J. , Vande Voorde Johan , Leung Hing Y.
Published: March 2023

Supplementary Data from Cyclocreatine Suppresses Creatine Metabolism and Impairs Prostate Cancer Progression
Supplementary Data from Aberrant Nuclear Export of circNCOR1 Underlies SMAD7-Mediated Lymph Node Metastasis of Bladder Cancer
Authors: An Mingjie , Zheng Hanhao , Huang Jian , Lin Yan , Luo Yuming , Kong Yao , Pang Mingrui , Zhang Dingwen , Yang Jiabin , Chen Jiancheng , Li Yuanlong , Chen Changhao , Lin Tianxin
Published: March 2023

Supplementary Data from Aberrant Nuclear Export of circNCOR1 Underlies SMAD7-Mediated Lymph Node Metastasis of Bladder Cancer
Supplementary Data from Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery
Authors: Gong Peijun , Chin Synn Lynn , Allen Wes M. , Ballal Helen , Anstie James D. , Chin Lixin , Ismail Hina M. , Zilkens Renate , Lakhiani Devina D. , McCarthy Matthew , Fang Qi , Firth Daniel , Newman Kyle , Thomas Caleb , Li Jiayue , Sanderson Rowan W. , Foo Ken Y. , Yeomans Chris , Dessauvagie Benjamin F. , Latham Bruce , Saunders Christobel M. , Kennedy Brendan F.
Published: March 2023

Supplementary Data from Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery
Supplementary Data from Therapeutic Targeting of Macrophage Plasticity Remodels the Tumor-Immune Microenvironment
Authors: Jang Hee-Jin , Lee Hyun-Sung , Yu Wendong , Ramineni Maheshwari , Truong Cynthia Y. , Ramos Daniela , Splawn Taylor , Choi Jong Min , Jung Sung Yun , Lee Ju-Seog , Wang Daniel Y. , Sederstrom Joel M. , Pietropaolo Massimo , Kheradmand Farrah , Amos Christopher I. , Wheeler Thomas M. , Ripley R. Taylor , Burt Bryan M.
Published: March 2023

Supplementary Data from Therapeutic Targeting of Macrophage Plasticity Remodels the Tumor-Immune Microenvironment
Supplementary Materials and Figure Legends from Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody–Drug Conjugates in Breast Cancer
Authors: Duro-Sánchez Santiago , Nadal-Serrano Mercedes , Lalinde-Gutiérrez Marta , Arenas Enrique Javier , Bernadó Morales Cristina , Morancho Beatriz , Escorihuela Marta , Pérez-Ramos Sandra , Escrivá-de-Romaní Santiago , Gandullo-Sánchez Lucía , Pandiella Atanasio , Esteve-Codina Anna , Rodilla Verónica , Dijcks Fred A. , Dokter Wim H.A. , Cortés Javier , Saura Cristina , Arribas Joaquín
Published: March 2023

Extended Materials and Methods and Supplementary figures with legends
Supplementary Figure S4 from Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody–Drug Conjugates in Breast Cancer
Authors: Duro-Sánchez Santiago , Nadal-Serrano Mercedes , Lalinde-Gutiérrez Marta , Arenas Enrique Javier , Bernadó Morales Cristina , Morancho Beatriz , Escorihuela Marta , Pérez-Ramos Sandra , Escrivá-de-Romaní Santiago , Gandullo-Sánchez Lucía , Pandiella Atanasio , Esteve-Codina Anna , Rodilla Verónica , Dijcks Fred A. , Dokter Wim H.A. , Cortés Javier , Saura Cristina , Arribas Joaquín
Published: March 2023

Effect of different inducers of senescence on the bystander effect of ADCs.
Supplementary Data from PRC2-Mediated Epigenetic Suppression of Type I IFN-STAT2 Signaling Impairs Antitumor Immunity in Luminal Breast Cancer
Authors: Hong Juyeong , Lee Ji Hoon , Zhang Zhao , Wu Yanming , Yang Mei , Liao Yiji , de la Rosa Richard , Scheirer Jessica , Pechacek Douglas , Zhang Nu , Xu Zhenming , Curiel Tyler , Tan Xi , Huang Tim H.-M. , Xu Kexin
Published: March 2023

Supplementary information
Supplementary Table 1 from Monounsaturated and Diunsaturated Fatty Acids Sensitize Cervical Cancer to Radiation Therapy
Authors: Muhammad Naoshad , Ruiz Fiona , Stanley Jennifer , Rashmi Ramachandran , Cho Kevin , Jayachandran Kay , Zahner Michael C. , Huang Yi , Zhang Jin , Markovina Stephanie , Patti Gary J. , Schwarz Julie K.
Published: March 2023

Tumor growth kinetics of SiHa xenograft tumors.
Supplementary Data from MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: Wu Chengyue , Jarrett Angela M. , Zhou Zijian , Elshafeey Nabil , Adrada Beatriz E. , Candelaria Rosalind P. , Mohamed Rania M.M. , Boge Medine , Huo Lei , White Jason B. , Tripathy Debu , Valero Vicente , Litton Jennifer K. , Yam Clinton , Son Jong Bum , Ma Jingfei , Rauch Gaiane M. , Yankeelov Thomas E.
Published: March 2023

Supplementary Data from MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Supplementary Figure 1 from Monounsaturated and Diunsaturated Fatty Acids Sensitize Cervical Cancer to Radiation Therapy
Authors: Muhammad Naoshad , Ruiz Fiona , Stanley Jennifer , Rashmi Ramachandran , Cho Kevin , Jayachandran Kay , Zahner Michael C. , Huang Yi , Zhang Jin , Markovina Stephanie , Patti Gary J. , Schwarz Julie K.
Published: March 2023

Differential effect of polyunsaturated fatty acid, Arachidonic acid (AA) in cervical cancer cells.
Supplementary Table 2 from N-myc–Mediated Translation Control Is a Therapeutic Vulnerability in Medulloblastoma
Authors: Kuzuoglu-Ozturk Duygu , Aksoy Ozlem , Schmidt Christin , Lea Robin , Larson Jon D. , Phelps Ryan R.L. , Nasholm Nicole , Holt Megan , Contreras Adrian , Huang Miller , Wong-Michalak Shannon , Shao Hao , Wechsler-Reya Robert , Phillips Joanna J. , Gestwicki Jason E. , Ruggero Davide , Weiss William A.
Published: March 2023

RPF abundance of Rapalink-1 and Rapamycin treated samples
Supplementary Data from Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models
Authors: Penter Livius , ten Hacken Elisa , Southard Jackson , Lareau Caleb A. , Ludwig Leif S. , Li Shuqiang , Neuberg Donna S. , Livak Kenneth J. , Wu Catherine J.
Published: March 2023

Supplementary Data from Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models
Table S9 from Integrative Single-Cell Analysis Reveals Transcriptional and Epigenetic Regulatory Features of Clear Cell Renal Cell Carcinoma
Authors: Yu Zhenyuan , Lv Yufang , Su Cheng , Lu Wenhao , Zhang RuiRui , Li Jiaping , Guo Bingqian , Yan Haibiao , Liu Deyun , Yang Zhanbin , Mi Hua , Mo Linjian , Guo Yi , Feng Wenyu , Xu Haotian , Peng Wenyi , Cheng Jiwen , Nan Aruo , Mo Zengnan
Published: March 2023

INDEL was detected by whole-exome sequencing of 19 ccRCC samples.
Table S19 from Integrative Single-Cell Analysis Reveals Transcriptional and Epigenetic Regulatory Features of Clear Cell Renal Cell Carcinoma
Authors: Yu Zhenyuan , Lv Yufang , Su Cheng , Lu Wenhao , Zhang RuiRui , Li Jiaping , Guo Bingqian , Yan Haibiao , Liu Deyun , Yang Zhanbin , Mi Hua , Mo Linjian , Guo Yi , Feng Wenyu , Xu Haotian , Peng Wenyi , Cheng Jiwen , Nan Aruo , Mo Zengnan
Published: March 2023

qPCR results of the expression of 4 deferent lncRNA in cytoplasm and nucleus. Three PCR by-wells were prepared for each sample.
Supplementary figures from ASPM Activates Hedgehog and Wnt Signaling to Promote Small Cell Lung Cancer Stemness and Progression
Authors: Cheng Li-Hsin , Hsu Chung-Chi , Tsai Hung-Wen , Liao Wen-Ying , Yang Pei-Ming , Liao Tai-Yan , Hsieh Hsiao-Yen , Chan Tze-Sian , Tsai Kelvin K.
Published: March 2023

This file contains Supplementary figures S1-S6
FigureS5 from Immunotherapeutic Targeting and PET Imaging of DLL3 in Small-Cell Neuroendocrine Prostate Cancer
Authors: Chou Jonathan , Egusa Emily A. , Wang Sinan , Badura Michelle L. , Lee Fei , Bidkar Anil P. , Zhu Jun , Shenoy Tanushree , Trepka Kai , Robinson Troy M. , Steri Veronica , Huang Jiaoti , Wang Yuzhuo , Small Eric J. , Chan Emily , Stohr Bradley A. , Ashworth Alan , Delafontaine Brant , Rottey Sylvie , Cooke Keegan S. , Hashemi Sadraei Nooshin , Yu Brian , Salvati Mark , Bailis Julie M. , Feng Felix Y. , Flavell Robert R. , Aggarwal Rahul
Published: March 2023

FigureS5
Figure S9 from Stromal Reprogramming through Dual PDGFRα/β Blockade Boosts the Efficacy of Anti–PD-1 Immunotherapy in Fibrotic Tumors
Authors: Akiyama Takahiko , Yasuda Tadahito , Uchihara Tomoyuki , Yasuda-Yoshihara Noriko , Tan Benjy J.Y. , Yonemura Atsuko , Semba Takashi , Yamasaki Juntaro , Komohara Yoshihiro , Ohnishi Koji , Wei Feng , Fu Lingfeng , Zhang Jun , Kitamura Fumimasa , Yamashita Kohei , Eto Kojiro , Iwagami Shiro , Tsukamoto Hirotake , Umemoto Terumasa , Masuda Mari , Nagano Osamu , Satou Yorifumi , Saya Hideyuki , Tan Patrick , Baba Hideo , Ishimoto Takatsugu
Published: March 2023

Supplementary Figure9
FigureS3 from Immunotherapeutic Targeting and PET Imaging of DLL3 in Small-Cell Neuroendocrine Prostate Cancer
Authors: Chou Jonathan , Egusa Emily A. , Wang Sinan , Badura Michelle L. , Lee Fei , Bidkar Anil P. , Zhu Jun , Shenoy Tanushree , Trepka Kai , Robinson Troy M. , Steri Veronica , Huang Jiaoti , Wang Yuzhuo , Small Eric J. , Chan Emily , Stohr Bradley A. , Ashworth Alan , Delafontaine Brant , Rottey Sylvie , Cooke Keegan S. , Hashemi Sadraei Nooshin , Yu Brian , Salvati Mark , Bailis Julie M. , Feng Felix Y. , Flavell Robert R. , Aggarwal Rahul
Published: March 2023

FigureS3
FigureS1 from Immunotherapeutic Targeting and PET Imaging of DLL3 in Small-Cell Neuroendocrine Prostate Cancer
Authors: Chou Jonathan , Egusa Emily A. , Wang Sinan , Badura Michelle L. , Lee Fei , Bidkar Anil P. , Zhu Jun , Shenoy Tanushree , Trepka Kai , Robinson Troy M. , Steri Veronica , Huang Jiaoti , Wang Yuzhuo , Small Eric J. , Chan Emily , Stohr Bradley A. , Ashworth Alan , Delafontaine Brant , Rottey Sylvie , Cooke Keegan S. , Hashemi Sadraei Nooshin , Yu Brian , Salvati Mark , Bailis Julie M. , Feng Felix Y. , Flavell Robert R. , Aggarwal Rahul
Published: March 2023

FigureS1
Supplementary Data from Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes and Extensive Intratumoral Heterogeneity
Authors: Williams Hannah L. , Dias Costa Andressa , Zhang Jinming , Raghavan Srivatsan , Winter Peter S. , Kapner Kevin S. , Ginebaugh Scott P. , Väyrynen Sara A. , Väyrynen Juha P. , Yuan Chen , Navia Andrew W. , Wang Junning , Yang Annan , Bosse Timothy L. , Kalekar Radha L. , Lowder Kristen E. , Lau Mai Chan , Elganainy Dalia , Morales-Oyarvide Vicente , Rubinson Douglas A. , Singh Harshabad , Perez Kimberly , Cleary James M. , Clancy Thomas E. , Wang Jiping , Mancias Joseph D. , Brais Lauren K. , Hill Emma R. , Kozak Margaret M. , Linehan David C. , Dunne Richard F. , Chang Daniel T. , Koong Albert C. , Hezel Aram F. , Hahn William C. , Shalek Alex K. , Aguirre Andrew J. , Nowak Jonathan A. , Wolpin Brian M.
Published: March 2023

Supplementary tables
Supplementary Data from Elevated Methionine Flux Drives Pyroptosis Evasion in Persister Cancer Cells
Authors: El-Kenawi Asmaa , Berglund Anders , Estrella Veronica , Zhang Yonghong , Liu Min , Putney Ryan M. , Yoder Sean J. , Johnson Joseph , Brown Joel , Gatenby Robert
Published: March 2023

Supplemental Figures S1-S6
Supplementary Movie S7 from Plk1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling
Authors: Patterson Jesse C. , Varkaris Andreas , Croucher Peter J.P. , Ridinger Maya , Dalrymple Susan , Nouri Mannan , Xie Fang , Varmeh Shohreh , Jonas Oliver , Whitman Matthew A. , Chen Sen , Rashed Saleh , Makusha Lovemore , Luo Jun , Isaacs John T. , Erlander Mark G. , Einstein David J. , Balk Steven P. , Yaffe Michael B.
Published: March 2023

Cellular division that occurred in a manner that was not parallel to the growth surface
Supplementary Data from CSN6 Mediates Nucleotide Metabolism to Promote Tumor Development and Chemoresistance in Colorectal Cancer
Authors: Zou Shaomin , Qin Baifu , Yang Ziqing , Wang Wencong , Zhang Jieping , Zhang Yijing , Meng Manqi , Feng Junyan , Xie Yunling , Fang Ling , Xiao Lishi , Zhang Peng , Meng Xiangqi , Choi Hyun Ho , Wen Weijie , Pan Qihao , Ghesquière Bart , Lan Ping , Lee Mong-Hong , Fang Lekun
Published: March 2023

Table S4
Supplementary Figures from Phagocytosis of Glioma Cells Enhances the Immunosuppressive Phenotype of Bone Marrow–Derived Macrophages
Authors: Wu Min , Wu Lingxiang , Wu Wei , Zhu Mengyan , Li Jianyu , Wang Ziyu , Li Jie , Ding Rong , Liang Yuan , Li Liangyu , Zhang Tingting , Huang Bin , Cai Yun , Li Kening , Li Lu , Zhang Rui , Hu Baoli , Lin Fan , Wang Xiuxing , Zheng Siyuan , Chen Jian , You Yongping , Jiang Tao , Zhang Junxia , Chen Hongshan , Wang Qianghu
Published: March 2023

Supplementary Figures S1-7
Supplemental Figure 1 from NFE2L2 Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells
Authors: Guan Li , Nambiar Dhanya K. , Cao Hongbin , Viswanathan Vignesh , Kwok Shirley , Hui Angela B. , Hou Yuan , Hildebrand Rachel , von Eyben Rie , Holmes Brittany J. , Zhao Junfei , Kong Christina S. , Wamsley Nathan , Zhang Weiruo , Major Michael B. , Seol Seung W. , Sunwoo John B. , Hayes D. Neil , Diehn Maximilian , Le Quynh-Thu
Published: March 2023

Mutational landscape and details of NFE2L2 gene mutation in a cohort of oral cavity cancer patients treated with surgery and postoperative (chemo)radiotherapy at Stanford University.
Supplementary Table S1 from METTL1-Mediated m7G tRNA Modification Promotes Lenvatinib Resistance in Hepatocellular Carcinoma
Authors: Huang Manling , Long Jianting , Yao Zhijia , Zhao Yi , Zhao Yutong , Liao Junbin , Lei Kai , Xiao Han , Dai Zihao , Peng Sui , Lin Shuibin , Xu Lixia , Kuang Ming
Published: March 2023

This file shows the antibodies used in the study.
Supplementary Figures from METTL1-Mediated m7G tRNA Modification Promotes Lenvatinib Resistance in Hepatocellular Carcinoma
Authors: Huang Manling , Long Jianting , Yao Zhijia , Zhao Yi , Zhao Yutong , Liao Junbin , Lei Kai , Xiao Han , Dai Zihao , Peng Sui , Lin Shuibin , Xu Lixia , Kuang Ming
Published: March 2023

This file describes supplementary figures.
Supplementary Table 3 from Androgen Signaling Contributes to Sex Differences in Cancer by Inhibiting NF-κB Activation in T Cells and Suppressing Antitumor Immunity
Authors: Zhang Xiaomin , Cheng Limin , Gao Chengqi , Chen Jing , Liao Shuangye , Zheng Yongqiang , Xu Liping , He Jingjing , Wang Danyang , Fang Ziqian , Zhang Jianeng , Yan Min , Luan Yi , Chen Siyu , Chen Likun , Xia Xiaojun , Deng Chunhao , Chen Guokai , Li Wende , Liu Zexian , Zhou Penghui
Published: March 2023

ATAC-seq Data
Figure S3 from PARP Inhibition Induces Synthetic Lethality and Adaptive Immunity in LKB1-Mutant Lung Cancer
Authors: Long Li-Li , Ma Si-Cong , Guo Ze-Qin , Zhang Yan-Pei , Fan Zhenzhen , Liu Li-Juan , Liu Li , Han Duan-Duan , Leng Meng-Xin , Wang Jian , Guo Xue-Jun , Tan Jia-Le , Cai Xiao-Ting , Lin Yan , Pan Xinghua , Wu De-Hua , Bai Xue , Dong Zhong-Yi
Published: March 2023

Overexpression of mutant PARP1 promotes activation of the IFNγ signaling pathway. (a, b) A549 lung cancer cells and LLC1 lung cancer cells were transfected with the catalytic mutant Flag-PARP1 (E988) followed by stimulation with IFNγ. The lysates were then subjected to western blot analysis for indicated proteins.
Supplementary Figure 1 from Androgen Signaling Contributes to Sex Differences in Cancer by Inhibiting NF-κB Activation in T Cells and Suppressing Antitumor Immunity
Authors: Zhang Xiaomin , Cheng Limin , Gao Chengqi , Chen Jing , Liao Shuangye , Zheng Yongqiang , Xu Liping , He Jingjing , Wang Danyang , Fang Ziqian , Zhang Jianeng , Yan Min , Luan Yi , Chen Siyu , Chen Likun , Xia Xiaojun , Deng Chunhao , Chen Guokai , Li Wende , Liu Zexian , Zhou Penghui
Published: March 2023

Supplementary Figure 1
Figure S1-S5, Table S1 from MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis
Authors: Wang Cheng-Kai , Chen Tzu-Jou , Tan Grace Y.T. , Chang Fang-Pei , Sridharan Samyuktha , Yu Chen-Hsin Albert , Chang Yen-Hou , Chen Yi-Jen , Cheng Li-Tzu , Hwang-Verslues Wendy W.
Published: March 2023

Table S1. Short tandem repeat of ovarian teratocarcinoma and clear cell carcinoma cell line.
Figure S1. MEX3A expression promoted tumorigenic ability and cell survival in WT p53 OC cells.
Figure S2. The p53 pathway was enriched in upregulated genes in MEX3A-depleted OC cells expressing WT p53.
Figure S3. Stabilized WT p53 protein in MEX3A-depleted cells was activated. MEX3A did not interact with or affect the level of mutant p53 protein.
Figure S4. p53 depletion alone did not significantly affect cell proliferation or cell death in MEX3A expressing WT p53 OC cells.
Figure S5. MEX3A and MDM2 in OC.
Supplementary table S3 from SMAD4 Loss Induces c-MYC–Mediated NLE1 Upregulation to Support Protein Biosynthesis, Colorectal Cancer Growth, and Metastasis
Authors: Loevenich Leon P. , Tschurtschenthaler Markus , Rokavec Matjaz , Silva Miguel G. , Jesinghaus Moritz , Kirchner Thomas , Klauschen Frederick , Saur Dieter , Neumann Jens , Hermeking Heiko , Jung Peter
Published: March 2023

Upregulated genes in SMAD4 mutant tumor organoid lines and DepMAP Project dependency scores.
Supplementary Figure S1-S8 from CircPDIA4 Induces Gastric Cancer Progression by Promoting ERK1/2 Activation and Enhancing Biogenesis of Oncogenic circRNAs
Authors: Shen Yue , Zhang Nasha , Chai Jie , Wang Teng , Ma Chi , Han Linyu , Yang Ming
Published: March 2023

Figure S1 shows elevated expression of circPDIA4 in gastric cancer tissues and impacts on viability of gastric cancer cells. Figure S2 shows that circPDIA4 enhanced invasive activities of gastric cancer cells. Figure S3 shows that circPDIA4 enhanced invasive activities of gastric cancer cells. Figure S4 shows that transcriptional factor SP1 plays an important role in up-regulating QKI expression in gastric cancer. Figure S5 shows that ERK1/2 interacts with circPDIA4 and phosphorylated ERK1/2 protein co-localizes with DUSP6 in gastric cancer. Figure S6 shows impacts of circPDIA4 on effects of different ERK inhibitors in gastric cancer. Figure S7 shows that silenced circPDIA4 promoted the suppression of cell viability induced by silencing of MAPK1 expression. Figure S8 shows that circPDIA4 facilitated oncogenic circRNAs formation depending on the RNA helicase DHX9 in gastric cancer.
Supplementary Fig-9 from The LncRNA LENOX Interacts with RAP2C to Regulate Metabolism and Promote Resistance to MAPK Inhibition in Melanoma
Authors: Gambi Giovanni , Mengus Gabrielle , Davidson Guillaume , Demesmaeker Ewout , Cuomo Alessandro , Bonaldi Tiziana , Katopodi Vicky , Malouf Gabriel G. , Leucci Eleonora , Davidson Irwin
Published: March 2023

Ectopic LENOX expression increases oxidative phosphorylation in HEKT cells
Supplementary Fig-4 from The LncRNA LENOX Interacts with RAP2C to Regulate Metabolism and Promote Resistance to MAPK Inhibition in Melanoma
Authors: Gambi Giovanni , Mengus Gabrielle , Davidson Guillaume , Demesmaeker Ewout , Cuomo Alessandro , Bonaldi Tiziana , Katopodi Vicky , Malouf Gabriel G. , Leucci Eleonora , Davidson Irwin
Published: March 2023

Gain of LENOX function stimulates melanoma cell proliferation
Suppl. Figure S2 from ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma
Authors: Eichhoff Ossia M. , Stoffel Corinne I. , Käsler Jan , Briker Luzia , Turko Patrick , Karsai Gergely , Zila Nina , Paulitschke Verena , Cheng Phil F. , Leitner Alexander , Bileck Andrea , Zamboni Nicola , Irmisch Anja , Balazs Zsolt , Tastanova Aizhan , Pascoal Susana , Johansen Pål , Wegmann Rebekka , Mena Julien , Othman Alaa , Viswanathan Vasanthi S. , Wenzina Judith , Aloia Andrea , Saltari Annalisa , Dzung Andreas , Krauthammer Michael , Schreiber Stuart L. , Hornemann Thorsten , Distel Martin , Snijder Berend , Dummer Reinhard , Levesque Mitchell P.
Published: March 2023

S2: HPLC analysis of STO13881 and nNeocuproine showed overlapping profiles and confirmed STO13881 to be neocuproine (purchased from Sigma-Aldrich, Switzerland). High-performance liquid chromatography (HPLC) analysis was performed using the Zuürich functional genomic center.
Suppl. Figure S15 from ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma
Authors: Eichhoff Ossia M. , Stoffel Corinne I. , Käsler Jan , Briker Luzia , Turko Patrick , Karsai Gergely , Zila Nina , Paulitschke Verena , Cheng Phil F. , Leitner Alexander , Bileck Andrea , Zamboni Nicola , Irmisch Anja , Balazs Zsolt , Tastanova Aizhan , Pascoal Susana , Johansen Pål , Wegmann Rebekka , Mena Julien , Othman Alaa , Viswanathan Vasanthi S. , Wenzina Judith , Aloia Andrea , Saltari Annalisa , Dzung Andreas , Krauthammer Michael , Schreiber Stuart L. , Hornemann Thorsten , Distel Martin , Snijder Berend , Dummer Reinhard , Levesque Mitchell P.
Published: March 2023

S15: Tumor response curves in mice for ionophoric copper-chelators in combination with binimetinib.
Suppl. Figure S10 from ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma
Authors: Eichhoff Ossia M. , Stoffel Corinne I. , Käsler Jan , Briker Luzia , Turko Patrick , Karsai Gergely , Zila Nina , Paulitschke Verena , Cheng Phil F. , Leitner Alexander , Bileck Andrea , Zamboni Nicola , Irmisch Anja , Balazs Zsolt , Tastanova Aizhan , Pascoal Susana , Johansen Pål , Wegmann Rebekka , Mena Julien , Othman Alaa , Viswanathan Vasanthi S. , Wenzina Judith , Aloia Andrea , Saltari Annalisa , Dzung Andreas , Krauthammer Michael , Schreiber Stuart L. , Hornemann Thorsten , Distel Martin , Snijder Berend , Dummer Reinhard , Levesque Mitchell P.
Published: March 2023

S10: Clinical data of orthologic slice cultures
Suppl. Figure S1 from ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma
Authors: Eichhoff Ossia M. , Stoffel Corinne I. , Käsler Jan , Briker Luzia , Turko Patrick , Karsai Gergely , Zila Nina , Paulitschke Verena , Cheng Phil F. , Leitner Alexander , Bileck Andrea , Zamboni Nicola , Irmisch Anja , Balazs Zsolt , Tastanova Aizhan , Pascoal Susana , Johansen Pål , Wegmann Rebekka , Mena Julien , Othman Alaa , Viswanathan Vasanthi S. , Wenzina Judith , Aloia Andrea , Saltari Annalisa , Dzung Andreas , Krauthammer Michael , Schreiber Stuart L. , Hornemann Thorsten , Distel Martin , Snijder Berend , Dummer Reinhard , Levesque Mitchell P.
Published: March 2023

S1: Evaluation of HST screening.
Data from Nitric Oxide Boosts Chemoimmunotherapy via Inhibition of Acid Sphingomyelinase in a Mouse Model of Melanoma
Authors: Perrotta Cristiana , Bizzozero Laura , Falcone Sestina , Rovere-Querini Patrizia , Prinetti Alessandro , Schuchman Edward H. , Sonnino Sandro , Manfredi Angelo A. , Clementi Emilio
Published: March 2023

Abstract
Cisplatin is one of the most effective anticancer drugs, but its severe toxic effects, including depletion of immune-competent cells, limit its efficacy. We combined the systemic treatment with cisplatin with intratumor delivery of dendritic cells (DC) previously treated ex vivo with a pulse of nitric oxide (NO) released by the NO donors (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1-ium-1,2-diolate or isosorbide dinitrate. We found that this chemoimmunotherapy, tested in the B16 mouse model of melanoma, was significantly more efficacious than cisplatin alone, leading to tumor regression and animal survival at low doses of cisplatin that alone had no effect. Tumor cure was not observed when combining cisplatin with DCs not exposed to NO donors, indicating the key role of the pretreatment with NO. We investigated the mechanisms responsible for the synergic effect of NO-treated DCs and cisplatin and found that NO-treated DCs were protected both in vitro and in vivo from cisplatin-induced cytotoxicity. Cisplatin triggered DC apoptosis through increased expression and activation of acid sphingomyelinase; pretreatment of DCs with NO donors prevented such activation and inhibited activation of the downstream proapoptotic events, including generation of ceramide, activation of caspases 3 and 9, and mitochondrial depolarization. The effects of NO were mediated through generation of its physiologic messenger, cyclic GMP. We conclude that NO and NO generating drugs represent promising tools to increase the efficacy of chemoimmunotherapies in vivo, promoting the survival and increasing the function of injected cells by targeting a key pathway in cisplatin-induced cytotoxicity. [Cancer Res 2007;67(16):7559–64]
Data from RING Domain–Mediated Interaction Is a Requirement for MDM2's E3 Ligase Activity
Authors: Kawai Hidehiko , Lopez-Pajares Vanessa , Kim Mihee M. , Wiederschain Dmitri , Yuan Zhi-Min
Published: March 2023

Abstract
The RING domain of MDM2 that is essential for its E3 ligase activity mediates binding to itself and its structural homologue MDMX. Whereas it has been reported that RING domain interactions are critical, it is not well understood how they affect the E3 ligase activity of MDM2. We report that the E3 ligase activity requires the RING domain–dependent complex formation. In vivo, MDM2 and MDMX hetero-RING complexes are the predominant form versus the MDM2 homo-RING complex. Importantly, the MDM2/MDMX hetero-RING complexes exhibit a greater E3 ligase activity than the MDM2 homo-RING complexes. Disruption of the binding between MDM2 and MDMX resulted in a marked increase in both abundance and activity of p53, emphasizing the functional importance of this heterocomplex in p53 control. [Cancer Res 2007;67(13):6026–30]
Data from Use of a Peptide Derived from Foot-and-Mouth Disease Virus for the Noninvasive Imaging of Human Cancer: Generation and Evaluation of 4-[18F]Fluorobenzoyl A20FMDV2 for In vivo Imaging of Integrin αvβ6 Expression with Positron Emission Tomography
Authors: Hausner Sven H. , DiCara Danielle , Marik Jan , Marshall John F. , Sutcliffe Julie L.
Published: March 2023

Abstract
Expression of the epithelial-specific integrin αvβ6 is low or undetectable in most adult tissues but may be increased during wound healing and inflammation and is up-regulated dramatically by many different carcinomas, making αvβ6 a promising target for the in vivo detection of cancer using noninvasive imaging. In addition, αvβ6 is recognized as promoting invasion and correlates with aggressive behavior of human cancers and thus agents that recognize αvβ6 specifically in vivo will be an essential tool for the future management of αvβ6-positive cancers. Recently, we identified the peptide NAVPNLRGDLQVLAQKVART (A20FMDV2), derived from foot-and-mouth disease virus, as a potent inhibitor of αvβ6. Using flow cytometry and ELISA, we show that this peptide is highly selective, inhibiting αvβ6-ligand binding with a IC50 of 3 nmol/L, an activity 1,000-fold more selective for αvβ6 than for other RGD-directed integrins (αvβ3, αvβ5, and α5β1). A20FMDV2 was radiolabeled on solid-phase using 4-[18F]fluorobenzoic acid, injected into mice bearing both αvβ6-negative and αvβ6-positive (DX3puro/DX3puroβ6 cell lines) xenografts and imaged using a small animal positron emission tomography (PET) scanner. Rapid uptake (<30 min) and selective retention (>5 h) of radioactivity in the αvβ6-positive versus the αvβ6-negative tumor, together with fast renal elimination of nonspecifically bound activity, resulted in specific imaging of the αvβ6-positive neoplasm. These data suggest that PET imaging of αvβ6-positive tumors is feasible and will provide an important new tool for early detection and improved management of many types of cancers. [Cancer Res 2007;67(16):7833–40]
Data from Role of Tumor Necrosis Factor-α and TRAIL in High-Dose Radiation–Induced Bystander Signaling in Lung Adenocarcinoma
Authors: Shareef Mohammed M. , Cui Nuan , Burikhanov Ravshan , Gupta Seema , Satishkumar Sabapathi , Shajahan Shahin , Mohiuddin Mohammed , Rangnekar Vivek M. , Ahmed Mansoor M.
Published: March 2023

Abstract
In the present study, ionizing radiation (IR)–induced bystander effects were investigated in two lung cancer cell lines. A549 cells were found to be more resistant to radiation-conditioned medium (RCM) obtained from A549 cells when compared with the H460 exposed to RCM procured from H460 cells. Significant release of tumor necrosis factor-α (TNF-α) was observed in A549 cells after IR/RCM exposure, and the survival was reversed with neutralizing antibody against TNF-α. In H460 cells, significant release of TNF-related apoptosis-inducing ligand (TRAIL), but not TNF-α, was observed in response to IR, RCM exposure, or RCM + 2Gy, and neutralizing antibody against TRAIL diminished clonogenic inhibition. Mechanistically, TNF-α present in RCM of A549 was found to mediate nuclear factor-κB (NF-κB) translocation to nucleus, whereas the soluble TRAIL present in RCM of H460 cells mobilized the nuclear translocation of PAR-4 (a proapoptotic protein). Analysis of IR-inducible early growth response-1 (EGR-1) function showed that EGR-1 was functional in A549 cells but not in H460 cells. A significant decrease in RCM-mediated apoptosis was observed in both A549 cells stably expressing small interfering RNA EGR-1 and EGR-1−/− mouse embryonic fibroblast cells. Thus, the high-dose IR-induced bystander responses in A549 may be dependent on the EGR-1 function and its target gene TNF-α. These findings show that the reduced bystander response in A549 cells is due to activation of NF-κB signaling by TNF-α, whereas enhanced response to IR-induced bystander signaling in H460 cells was due to release of TRAIL associated with nuclear translocation of PAR-4. [Cancer Res 2007;67(24):11811–20]
Data from The Original Pathologische Anatomie Leiden-Endothelium Monoclonal Antibody Recognizes a Vascular Endothelial Growth Factor–Binding Site within Neuropilin-1
Authors: Jaalouk Diana E. , Ozawa Michael G. , Sun Jessica , Lahdenranta Johanna , Schlingemann Reinier O. , Pasqualini Renata , Arap Wadih
Published: March 2023

Abstract
For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display–based approach (“epitope mapping”) to select peptides binding to the original PAL-E antibody. We found that a subset of the selected panel of peptides had motifs with strong homology to an exposed site within the b1 domain of human neuropilin-1 (NRP-1). We confirmed peptide binding by ELISA and by surface plasmon resonance. We also showed that the PAL-E antigen colocalizes with NRP-1 staining in endothelial cells. Crystal structure of the b1 domain in NRP-1 suggests that the PAL-E binding site overlaps with a vascular endothelial growth factor (VEGF) binding site. Taken together, these results indicate that NRP-1 is an endothelial cell antigen recognized by the true PAL-E antibody. The consistent biochemical, morphologic, and functional features between the PAL-E antigen and NRP-1 support our interpretation. Given that NRP-1 is a VEGF receptor, these results explain the attributes of the PAL-E antibody as a marker of vascular permeability and angiogenesis. [Cancer Res 2007;67(20):9623–9]
Data from High SEPT9_v1 Expression in Human Breast Cancer Cells Is Associated with Oncogenic Phenotypes
Authors: Gonzalez Maria E. , Peterson Esther A. , Privette Lisa M. , Loffreda-Wren Janice L. , Kalikin Linda M. , Petty Elizabeth M.
Published: March 2023

Abstract
Altered expression of the human septin gene, SEPT9, and its murine homologue, Sept9, has been implicated in neoplasia. However, their role(s) in oncogenesis remains poorly understood. We found amplification of SEPT9 in 67% of breast cancer cells (BCC) when compared with immortalized human mammary epithelial cells (IHMEC) as well as high levels of SEPT9 expression in the majority (61%) of the BCCs studied, unlike IHMECs. Expression profiling of variant SEPT9 transcripts and translated products revealed that high expression of the variant, SEPT9_v1, in contrast to other variants, was widespread in BCCs (55% of the BCCs) but not in IHMECs. High expression of SEPT9_v1 was also observed in primary breast cancer samples by immunohistochemical studies. We subsequently examined the phenotypic consequences of SEPT9_v1 expression in human breast cells. Retroviral expression of SEPT9_v1 in IHMEC cell culture models showed that SEPT9_v1 accelerated growth kinetics, stimulated cell motility, promoted invasion in Matrigel Transwell assays, increased genomic instability with the development of aneuploidy, and stimulated morphologic changes. Significant cytokinesis defects and disruption of tubulin microfilaments were also observed by immunofluorescence when SEPT9_v1 was ectopically expressed in IHMECs. Furthermore, SEPT9_v1 markedly enhanced neoplastic transformation in Hs578T cells, a BCC with no endogenous expression of the SEPT9_v1 isoform. Small interfering RNA–mediated and short hairpin RNA–mediated inhibition of SEPT9_v1 expression in two BCCs with high levels of endogenous SEPT9_v1 expression inhibited neoplastic growth properties of the cells. Taken together, our findings suggest that increased SEPT9_v1 expression contributes to the malignant pathogenesis of some breast tumors. [Cancer Res 2007;67(18):8554–11]
Data from Fms-like Tyrosine Kinase 3 Ligand Stimulation Induces MLL-Rearranged Leukemia Cells into Quiescence Resistant to Antileukemic Agents
Authors: Furuichi Yoshiyuki , Goi Kumiko , Inukai Takeshi , Sato Hiroki , Nemoto Atsushi , Takahashi Kazuya , Akahane Koshi , Hirose Kinuko , Honna Hiroko , Kuroda Itaru , Zhang Xiaochun , Kagami Keiko , Hayashi Yasuhide , Harigaya Kenichi , Nakazawa Shinpei , Sugita Kanji
Published: March 2023

Abstract
Fms-like tyrosine kinase 3 (FLT3) is highly expressed in acute lymphoblastic leukemia with the mixed-lineage leukemia (MLL) gene rearrangement refractory to chemotherapy. We examined the biological effect of FLT3-ligand (FL) on 18 B-precursor leukemic cell lines with variable karyotypic abnormalities, and found that nine of nine MLL-rearranged cell lines with wild-type FLT3, in contrast to other leukemic cell lines, are significantly inhibited in their proliferation in a dose-dependent manner by FL. This inhibition was due to induction of the G0-G1 arrest. A marked up-regulation of p27 by suppression of its protein degradation and an abrogation of constitutive signal transducers and activators of transcription 5 phosphorylation were revealed in arrested leukemia cells after FL stimulation. Importantly, FL treatment rendered not only cell lines but also primary leukemia cells with MLL rearrangement resistant to chemotherapeutic agents. MLL-rearranged leukemia cells adhering to the bone marrow stromal cell line, which expresses FL as the membrane-bound form, were induced to quiescent state resistant to chemotherapeutic agents, but their chemosensitivity was significantly restored in the presence of neutralizing anti-FL antibody. The FL/FLT3 interaction between leukemia cells and bone marrow stromal cells expressing FL at high levels should contribute, at least in part, to persistent minimal-residual disease of MLL-rearranged leukemia in bone marrow. [Cancer Res 2007;67(20):9852–61]
Data from Glutathione S-Transferase P1: Gene Sequence Variation and Functional Genomic Studies
Authors: Moyer Ann M. , Salavaggione Oreste E. , Wu Tse-Yu , Moon Irene , Eckloff Bruce W. , Hildebrandt Michelle A.T. , Schaid Daniel J. , Wieben Eric D. , Weinshilboum Richard M.
Published: March 2023

Abstract
Glutathione S-transferase P1 (GSTP1) is of importance for cancer research because of its role in detoxifying carcinogens, activating antineoplastic prodrugs, metabolizing chemotherapeutic agents, and its involvement in cell cycle and apoptosis regulation. Two common GSTP1 genetic polymorphisms have been studied extensively. However, the full range of GSTP1 genetic variation has not been systematically characterized in the absence of disease pathology. We set out to identify common GSTP1 polymorphisms in four ethnic groups, followed by functional genomic studies. All exons, splice junctions, and the 5′-flanking region of GSTP1 were resequenced using 60 DNA samples each from four ethnic groups. The 35 single-nucleotide polymorphisms (SNP) identified included six nonsynonymous SNPs and 17 previously unreported polymorphisms. GSTP1 variant allozymes were then expressed in COS-1 cells, and five displayed significantly altered levels of enzyme activity. One decreased to 22% of the wild-type (WT) activity. Four variant allozymes had Km values that differed significantly from that of the WT, and five showed altered levels of immunoreactive protein compared with WT, with a significant correlation (r = 0.79, P < 0.007) between levels of immunoreactive protein and enzyme activity in these samples. In the Mexican American population, five linked SNPs were significantly associated with GSTP1 mRNA expression, one of which was found by electrophoretic mobility shift assay to alter protein binding. These studies have identified functionally significant genetic variation, in addition to the two frequently studied GSTP1 nonsynonymous SNPs, that may influence GSTP1's contribution to carcinogen and drug metabolism, and possibly disease pathogenesis and/or drug response. [Cancer Res 2008;68(12):4791–801]
Data from Gain of Oncogenic Function of p53 Mutants Induces Invasive Phenotypes in Human Breast Cancer Cells by Silencing CCN5/WISP-2
Authors: Dhar Gopal , Banerjee Snigdha , Dhar Kakali , Tawfik Ossama , Mayo Matthew S. , VanVeldhuizen Peter J. , Banerjee Sushanta K.
Published: March 2023

Abstract
CCN5/WISP-2 is overexpressed in noninvasive breast cancer cells and tissue samples, whereas its expression is minimal or undetected in invasive conditions. CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. However, the mechanism of silencing of CCN5 during the progression of the disease has been elusive. Because p53 mutations are associated with breast cancer progression and have been shown to correlate inversely with CCN5/WISP-2 expression in other cancer cell types, the objective of this study was to explore whether p53 mutants suppress CCN5 expression in breast tumor cells resulting in the progression of this disease. We found CCN5 expression is inversely correlated with the mutational activation of p53 in human breast tumor cells. The ectopic expression of p53 mutants in ER-positive noninvasive breast tumor cells silenced the CCN5/WISP-2 expression and enhanced invasive phenotypes, including the induction of morphologic changes from the epithelial-to-mesenchymal type along with the alterations of hallmark proteins of these cell types and an augmentation of the migration of these cells. The suppression of CCN5 by the p53 mutants can be nullified by estrogen signaling in these cells through the transcriptional activation of the CCN5 gene. Moreover, the invasive changes can be imitated by blocking the CCN5/WISP-2 expression through RNA interference or can be reversed by the addition of CCN5/WISP-2 recombinant protein in the culture. Thus, these studies suggest that CCN5 inactivation could be an essential molecular event for p53 mutant–induced invasive phenotypes. [Cancer Res 2008;68(12):4580–7]
Data from Molecular Basis for the Induction of an Angiogenesis Inhibitor, Thrombospondin-1, by 5-Fluorouracil
Authors: Zhao Hong-Ye , Ooyama Akio , Yamamoto Masatatsu , Ikeda Ryuji , Haraguchi Misako , Tabata Sho , Furukawa Tatsuhiko , Che Xiao-Fang , Zhang Shaoxuan , Oka Toshinori , Fukushima Masakazu , Nakagawa Masayuki , Ono Mayumi , Kuwano Michihiko , Akiyama Shin-ichi
Published: March 2023

Abstract
5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in chemotherapy against various solid tumors. 5-FU dose-dependently increased the expression levels of intrinsic antiangiogenic factor thrombospondin-1 (TSP-1) in human colon carcinoma KM12C cells and human breast cancer MCF7 cells. We investigated the molecular basis for the induction of TSP-1 by 5-FU in KM12C cells. Promoter assays showed that the region with the Egr-1 binding site is critical for the induction of TSP-1 promoter activity by 5-FU. The binding of Egr-1 to the TSP-1 promoter was increased in KM12C cells treated with 5-FU. Immunofluorescence staining revealed that 5-FU significantly increased the level of Egr-1 in the nuclei of KM12C cells. The suppression of Egr-1 expression by small interfering RNA decreased the expression level of TSP-1. Furthermore, 5-FU induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and heat shock protein 27 (HSP27). Blockade of the p38 MAPK pathway by SB203580 remarkably inhibited the phosphorylation of HSP27 induced by 5-FU and decreased the induction of Egr-1 and TSP-1 by 5-FU in KM12C cells. These findings suggest that the p38 MAPK pathway plays a crucial role in the induction of Egr-1 by 5-FU and that induced Egr-1 augments TSP-1 promoter activity, with the subsequent production of TSP-1 mRNA and protein. [Cancer Res 2008;68(17):7035–41]