bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S3 from TRIM50 inhibits gastric cancer progression by regulating the ubiquitination and nuclear translocation of JUP
Authors: Hu Jiajia , Huang Runjie , Liang Chengcai , Wang Yingnan , Wang Min , Chen Yanxing , Wu Chenyi , Zhang Jinling , Liu Zekun , Zhao Qi , Liu Zexian , Wang Feng , Yuan Shuqiang
Published: September 2024

Figure S3A: Tumor photograph in the nude mouse subcutaneous xenograft model by implanting TRIM50 overexpressing (TRIM50) versus control empty vector (EV) MKN45 cells (n = 6 mice per group). Scale bar: 1 cm
Figure S3B: MKN74 cells were transfected with lentiviruses expressing TRIM50 shRNA. A universal nonsilencing shRNA was used as a negative control (sh-NC). Whole-cell lysates were subjected to immunoblot analysis with TRIM50 antibody.
Figure S3C: Tumor photograph in the nude mouse subcutaneous xenograft model by implanting TRIM50 knockdown (TRIM50 sh-1/TRIM50 sh-2) versus control (TRIM50 sh-NC) MKN74 cells (n = 6 mice per group). Scale bar: 1 cm
Supplementary Figure 4 from Podoplanin drives amoeboid invasion in canine and human mucosal melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: September 2024

Loss of PDPN leads to cell cycle arrest and cellular senescence.
Supplementary Figure 2 from Podoplanin drives amoeboid invasion in canine and human mucosal melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: September 2024

PDPN regulates canine mucosal melanoma proliferation, survival, migration, and invasion.
Supplementary Table 6 from Telomerase upregulation induces progression of mouse BrafV600E-driven thyroid cancers and triggers non-telomeric effects
Authors: Landa Inigo , Thornton Caitlin EM , Xu Bin , Haase Jacob , Krishnamoorthy Gnana P. , Hao Jingzhu , Knauf Jeffrey A. , Herbert Zachary T. , Martínez Paula , Blasco Maria A. , Ghossein Ronald , Fagin James A.
Published: September 2024

Full list of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis “up terms” for the BrafV600E vs. BrafV600E+Tert-123C>T comparison.
Supplementary Table 3 from Telomerase upregulation induces progression of mouse BrafV600E-driven thyroid cancers and triggers non-telomeric effects
Authors: Landa Inigo , Thornton Caitlin EM , Xu Bin , Haase Jacob , Krishnamoorthy Gnana P. , Hao Jingzhu , Knauf Jeffrey A. , Herbert Zachary T. , Martínez Paula , Blasco Maria A. , Ghossein Ronald , Fagin James A.
Published: September 2024

Differentially expressed genes from RNAseq data
Supplementary Figure 5 from Telomerase upregulation induces progression of mouse BrafV600E-driven thyroid cancers and triggers non-telomeric effects
Authors: Landa Inigo , Thornton Caitlin EM , Xu Bin , Haase Jacob , Krishnamoorthy Gnana P. , Hao Jingzhu , Knauf Jeffrey A. , Herbert Zachary T. , Martínez Paula , Blasco Maria A. , Ghossein Ronald , Fagin James A.
Published: September 2024

In vivo dabrafenib plus trametinib treatment of mice.
Supplementary Figure 3 from Telomerase upregulation induces progression of mouse BrafV600E-driven thyroid cancers and triggers non-telomeric effects
Authors: Landa Inigo , Thornton Caitlin EM , Xu Bin , Haase Jacob , Krishnamoorthy Gnana P. , Hao Jingzhu , Knauf Jeffrey A. , Herbert Zachary T. , Martínez Paula , Blasco Maria A. , Ghossein Ronald , Fagin James A.
Published: September 2024

Additional insights from RNAscope analysis and telomere length evaluation. A-L. Analysis of intratumoral heterogeneity of Tert transcription via RNAscope.
Supplementary Data File S1 from USP1 expression driven by EWS::FLI1 transcription factor stabilizes Survivin and mitigates replication stress in Ewing sarcoma
Authors: Mallard Halle J. , Wan Shibiao , Nidhi Prakriti , Hanscom-Trofy Yvan D. , Mohapatra Bhopal , Woods Nicholas T. , Lopez-Guerrero Jose Antonio , Llombart-Bosch Antonio , Machado Isidro , Scotlandi Katia , Kreiling Natasha F. , Perry Megan C. , Mirza Sameer , Coulter Donald W. , Band Vimla , Band Hamid , Ghosal Gargi
Published: September 2024

RT-qPCR array of DUBs. RQ values of EWS cell lines normalized to GAPDH, represented as fold change relative to hMSC.
Figure S7 from CBF-beta mitigates PI3K-alpha-specific inhibitor killing through PIM1 in PIK3CA mutant gastric cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: September 2024

Figure S7 shows loss of PIM1 re-sensitizes resistant cells to BYL719
Figure S5 from CBF-beta mitigates PI3K-alpha-specific inhibitor killing through PIM1 in PIK3CA mutant gastric cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: September 2024

Figure S5 shows BH3 mimetics and MCL1 modifiers in combination with BYL719
Figure S1 from CBF-beta mitigates PI3K-alpha-specific inhibitor killing through PIM1 in PIK3CA mutant gastric cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: September 2024

Figure S1 shows BYL719 and DMSO beta scores calculated by the MAGeCK analysis pipeline
Table S5 from Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: September 2024

Secretome
Table S4 from Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: September 2024

Metabolism pathways
Table S3 from Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: September 2024

Multivariate Analysis
Table S2 from Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: September 2024

Patient cohort
Figure S5 from Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: September 2024

Stromal cell expression of DDR2 is critical for migration and invasion of ovarian cancer cells, related to Figure 7
Figure S3 from Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: September 2024

Stromal cell expression of DDR2 is critical for migration of ovarian cancer cells, related to Figure 4
Figure S1 from Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: September 2024

Mouse ovarian cancer cell line ID8Trp53-/-Brca2-/- express DDR2. Related to Figure 2
Supplementary Table 1 from Exon junction complex mediates the cap-independent translation of circular RNA
Authors: Lin Hui-Hsuan , Chang Chiu-Yuan , Huang Yi-Ren , Shen Che-Hung , Wu Yu-Chen , Chang Kai-Li , Lee Yueh-Chun , Lin Ya-Chi , Ting Wen-Chien , Chien Han-Ju , Zheng Yi-Feng , Lai Chien-Chen , Hsiao Kuei-Yang
Published: September 2024

Sequences
Supplementary Figure 7 from Competing engagement of β-arrestin isoforms balances IGF1R/p53 signaling and controls melanoma cell chemotherapeutic responsiveness
Authors: Cismas Sonia , Pasca Sylvya , Crudden Caitrin , Troccoli Drakensjo Iara , Suleymanova Naida , Zhang Simin , Gebhard Benjamin , Song Dawei , Neo Shiyong , Shibano Takashi , Smith Terry J. , Calin George A. , Girnita Ada , Girnita Leonard
Published: September 2024

Effect of combination treatment on p53-activation in skin melanoma malignant phenotype in in vitro 3D models
Supplementary Figure 4 from Competing engagement of β-arrestin isoforms balances IGF1R/p53 signaling and controls melanoma cell chemotherapeutic responsiveness
Authors: Cismas Sonia , Pasca Sylvya , Crudden Caitrin , Troccoli Drakensjo Iara , Suleymanova Naida , Zhang Simin , Gebhard Benjamin , Song Dawei , Neo Shiyong , Shibano Takashi , Smith Terry J. , Calin George A. , Girnita Ada , Girnita Leonard
Published: September 2024

Effect of β-arrestin imbalance on IGF1R expression
Data from Downregulation of BASP1 promotes temozolomide resistance in gliomas via epigenetic activation of the FBXO32/NF-κB/MGMT axis
Authors: Liao Xinyi , Li Ziwen , Zheng Haiqing , Qian Wanying , Zhang Shuxia , Chen Suwen , Li Xincheng , Tang Miaoling , Xu Yingru , Yu Ruyuan , Li Man , Song Libing , Li Jun
Published: September 2024

Abstract
The chemoresistance of temozolomide (TMZ)-based therapy is a serious limitation for lasting effective treatment of gliomas, while the underlying mechanisms remain unclear. In this study, we showed that downregulation of BASP1 correlated negatively with the response to TMZ therapy and disease-free survival of patients with gliomas. Silencing BASP1 significantly enhanced the TMZ-resistance of glioma cells both in vitro and in vivo through repair of TMZ-induced DNA damage via activation of the FBXO32/NF-κB/MGMT axis in both MGMT methylated and unmethylated gliomas. We demonstrated that loss of BASP1 resulted in removal of TRIM37/EZH2 complex-induced repressive histone modifications, including H2A-ub and H3K27me3, but addition of WDR5/MLL complex-mediated active histone modifications, including H3K4me3 and H3K9ac, on the FBXO32 promoter, which elicited in FBXO32 upregulation and further activated NF-κB/MGMT signaling via ubiquitin-dependent degradation of IκBα. Importantly, treatment with OICR-9429, an antagonist of the WDR5-MLL interaction, impaired the FBXO32/NF-κB/MGMT axis-mediated repair of TMZ-induced DNA damage, leading to significant apoptosis of BASP1-downregulated glioma cells. These findings shed light on the molecular mechanism underlying BASP1-mediated epigenetic transcriptional repression and may represent a potential strategy in the fight against TMZ-resistant gliomas.
Implications: BASP1 downregulation promotes TMZ resistance in gliomas through WDR5/MLL complex-mediated epigenetic activation of the FBXO32/NF-κB/MGMT axis, providing new target for improving outcomes in patients with TMZ-resistant gliomas.
Data from USP10 regulates ZEB1 ubiquitination and protein stability to inhibit ZEB1-mediated colorectal cancer metastasis
Authors: Sun Lei , Yu Jia , Guinney Justin , Qin Bo , Sinicrope Frank A.
Published: September 2024

Abstract
Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that can promote tumor invasion and metastasis by inducing epithelial to mesenchymal transition (EMT). To date, regulation of ZEB1 by RAS/RAF signaling remains unclear, and few studies have examined post translation modification of ZEB1 including its ubiquitination. In human colorectal cancer (CRC) cell lines with RAS/RAF/MEK/ERK activation, an interaction of ZEB1 with the deubiquitinase ubiquitin-specific protease 10 (USP10) was identified whereby USP10 modifies ZEB1 ubiquitination and promotes its proteasomal degradation. Regulation of the USP10-ZEB1 interaction by MEK-ERK signaling was shown whereby constitutive activation of ERK can phosphorylate USP10 at Ser236 to impair its interaction with ZEB1 and enable ZEB1 protein stabilization. Stabilized ZEB1 was shown to promote CRC metastatic colonization in a mouse tail vein injection model. Conversely, MEK-ERK inhibition blocked USP10 phosphorylation and enhanced the USP10-ZEB1 interaction shown to suppress ZEB1-mediated tumor cell migration and metastasis. In conclusion, we demonstrate a novel function of USP10 in the regulation of ZEB1 protein stability and its ability to mediate tumor metastasis in a preclinical model.

Implications: The MEK-ERK regulated interaction of USP10 with ZEB1 can promote the proteasomal degradation of ZEB1 and thereby suppress its demonstrated ability to mediate tumor metastasis.
Data from FOXA1 reprogramming dictates retinoid X receptor response in ESR1 mutant breast cancer
Authors: Wu Yang , Li Zheqi , Wedn Abdalla M. , Casey Allison N. , Brown Daniel , Rao Shalini V. , Omarjee Soleilmane , Hooda Jagmohan , Carroll Jason S. , Gertz Jason , Atkinson Jennifer M. , Lee Adrian V. , Oesterreich Steffi
Published: September 2024

Abstract
Estrogen receptor alpha (ER/ESR1) mutations occur in 30-40% of endocrine resistant ER-positive (ER+) breast cancer. Forkhead Box A1 (FOXA1) is a key pioneer factor mediating ER-chromatin interactions and endocrine response in ER+ breast cancer, but its role in ESR1 mutant breast cancer remains unclear. Our previous FOXA1 ChIP-seq identified a large portion of redistributed binding sites in T47D genome-edited Y537S and D538G ESR1 mutant cells. Here, we further integrated FOXA1 genomic binding profile with the isogenic ER cistrome, accessible genome and transcriptome data of T47D cell model. FOXA1 redistribution was significantly associated with transcriptomic alterations caused by ESR1 mutations. Furthermore, in ESR1 mutant cells, FOXA1 binding sites less frequently overlapped with ER, and differential gene expression was less associated with the canonical FOXA1-ER axis. Motif analysis revealed a unique enrichment of retinoid X receptor (RXR) motifs in FOXA1 binding sites of ESR1 mutant cells. Consistently, ESR1 mutant cells were more sensitive to growth stimulation with the RXR agonist LG268. The mutant-specific response was dependent on two RXR isoforms, RXR-α and RXR-β, with a stronger dependency on the latter. In addition, T3, the agonist of thyroid receptor also showed a similar growth-promoting effect in ESR1 mutant cells. Importantly, RXR antagonist HX531 blocked growth of ESR1 mutant cells and a patient derived xenograft (PDX)-derived organoid with an ESR1 D538G mutation. Collectively, our data support evidence for a stronger RXR response associated with FOXA1 reprogramming in ESR1 mutant cells, suggesting development of therapeutic strategies targeting RXR pathways in breast tumors with ESR1 mutation.
Implications: It provides comprehensive characterization of the role of FOXA1 in ESR1 mutant breast cancer and potential therapeutic strategy through blocking RXR activation.
Data from Disruption of the MYC Super-Enhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: September 2024

Abstract
Mutations in Fms-like tyrosine kinase 3 (FLT3) are common drivers in acute myeloid leukemia (AML) yet FLT3 inhibitors only provide modest clinical benefit. Prior work has shown that inhibitors of lysine-specific demethylase 1 (LSD1) enhance kinase inhibitor activity in AML. Here we show that combined LSD1 and FLT3 inhibition induces synergistic cell death in FLT3-mutant AML. Multi-omic profiling revealed that the drug combination disrupts STAT5, LSD1, and GFI1 binding at the MYC blood super-enhancer, suppressing super-enhancer accessibility as well as MYC expression and activity. The drug combination simultaneously results in the accumulation of repressive H3K9me1 methylation, an LSD1 substrate, at MYC target genes. We validated these findings in 72 primary AML samples with the nearly every sample demonstrating synergistic responses to the drug combination. Collectively, these studies reveal how epigenetic therapies augment the activity of kinase inhibitors in FLT3-ITD AML.

Implications: This work establishes the synergistic efficacy of combined FLT3 and LSD1 inhibition in FLT3-ITD AML by disrupting STAT5 and GFI1 binding at the MYC blood-specific super-enhancer complex.
Data from Non-essential amino acid availability influences proteostasis and breast cancer cell survival during proteotoxic stress
Authors: Sannino Sara , Manuel Allison M. , Shang Chaowei , Wendell Stacy G. , Wipf Peter , Brodsky Jeffrey L.
Published: September 2024

Abstract
Protein homeostasis (proteostasis) regulates tumor growth and proliferation when cells are exposed to proteotoxic stress, such as during treatment with certain chemotherapeutics. Consequently, cancer cells depend to a greater extent on stress signaling, and require the integrated stress response (ISR), amino acid metabolism, and efficient protein folding and degradation pathways to survive. To define how these interconnected pathways are wired when cancer cells are challenged with proteotoxic stress, we investigated how amino acid abundance influences cell survival when Hsp70, a master proteostasis regulator, is inhibited. We previously demonstrated that cancer cells exposed to a specific Hsp70 inhibitor induce the ISR via the action of two sensors, GCN2 and PERK, in stress-resistant and sensitive cells, respectively. In resistant cells, the induction of GCN2 and autophagy supported resistant cell survival, yet the mechanism by which these events were induced remained unclear. We now report that amino acid availability reconfigures the proteostasis network. Amino acid supplementation, and in particular arginine addition, triggered cancer cell death by blocking autophagy. Consistent with the importance of amino acid availability, which when limited activates GCN2, resistant cancer cells succumbed when challenged with a potentiator for another amino acid sensor, mTORC1, in conjunction with Hsp70 inhibition.
Implications: These data position amino acid abundance, GCN2, mTORC1, and autophagy as integrated therapeutic targets whose coordinated modulation regulates the survival of proteotoxic-resistant breast cancer cells.
Data from Tumor-derived CCL5 recruits cancer-associated fibroblasts and promotes tumor cell proliferation in esophageal squamous cell carcinoma
Authors: Dunbar Karen J. , Karakasheva Tatiana A. , Tang Qiaosi , Efe Gizem , Lin Eric W. , Harris Michael , Sahu Varun , Sachdeva Uma M. , Hu Jianhua , Klein-Szanto Andres J. , Henick Brian , Diehl J. Alan , Nakagawa Hiroshi , Rustgi Anil K.
Published: September 2024

Abstract
Cancer-associated fibroblasts (CAFs) can promote tumor growth, metastasis and therapeutic resistance in esophageal squamous cell carcinoma (ESCC), but the mechanisms of action remain elusive. Our objective was to identify secreted factor(s) that mediate the communication between CAFs and ESCC tumor cells with the aim of identifying potential druggable targets. Through unbiased cytokine arrays, we have identified CC motif chemokine ligand 5 (CCL5) as a secreted factor that is increased upon co-culture of ESCC cells and CAFs, which we replicated in esophageal adenocarcinoma (EAC) with CAFs. Loss of tumor-cell derived CCL5 reduces ESCC cell proliferation in vitro and in vivo and we propose this is mediated, in part, by a reduction in ERK1/2 signaling. Loss of tumor-derived CCL5 reduces the percentage of CAFs recruited to xenograft tumors in vivo. CCL5 is a ligand for the CC motif receptor 5 (CCR5), for which a clinically approved inhibitor exists, namely Maraviroc. Maraviroc treatment reduced tumor volume, CAF recruitment and ERK1/2 signaling in vivo, thus, mimicking the effects observed with genetic loss of CCL5. High CCL5 or CCR5 expression is associated with worse prognosis in low grade esophageal carcinomas.

Implications: These data highlight the role of CCL5 in tumorigenesis and the therapeutic potential of targeting the CCL5-CCR5 axis in ESCC.
Data from Fibronectin contributes to a BRAF inhibitor-driven invasive phenotype in thyroid cancer through EGR1, which can be blocked by inhibition of ERK1/2.
Authors: Hicks Hannah M. , Pozdeyev Nikita , Sams Sharon B. , Pugazhenthi Umarani , Bales Elise S. , Hofmann Marie-Claude , McKenna Logan R. , Schweppe Rebecca E.
Published: September 2024

Abstract
Mutations in BRAF are common in advanced papillary and anaplastic thyroid cancer (PTC and ATC). However, BRAF-mutant PTC patients currently lack therapies targeting this pathway. Despite the approved combination of BRAF and MEK1/2 inhibition for patients with BRAF-mutant ATC, these patients often progress. Thus, we screened a panel of BRAF-mutant thyroid cancer cell lines to identify new therapeutic strategies. We showed that thyroid cancer cells resistant to BRAF inhibition (BRAFi) exhibit an increase in invasion and a pro-invasive secretome in response to BRAFi. Using Reverse Phase Protein Array (RPPA), we identified a nearly 2-fold increase in expression of the extracellular matrix protein, fibronectin, in response to BRAFi treatment, and a corresponding 1.8 to 3.0-fold increase in fibronectin secretion. Accordingly, the addition of exogenous fibronectin phenocopied the BRAFi-induced increase in invasion while depletion of fibronectin in resistant cells resulted in loss of increased invasion. We further showed that BRAFi-induced invasion can be blocked by inhibition of ERK1/2. In a BRAFi-resistant patient-derived xenograft model, we found that dual inhibition of BRAF and ERK1/2 slowed tumor growth and decreased circulating fibronectin. Using RNA-sequencing, we identified EGR1 as a top downregulated gene in response to combined BRAF/ERK1/2 inhibition, and we further showed that EGR1 is necessary for a BRAFi-induced increase in invasion and for induction of fibronectin in response to BRAFi.
Implications: Together, these data show that increased invasion represents a new mechanism of resistance to BRAF inhibition in thyroid cancer that can be targeted with an ERK1/2 inhibitor.
Data from Identification of a ΔNp63-Dependent Basal-Like A Subtype-Specific Transcribed Enhancer Program (B-STEP) in Aggressive Pancreatic Ductal Adenocarcinoma
Authors: Wang Xin , Kutschat Ana P. , Aggrey-Fynn Joana , Hamdan Feda H. , Graham Rondell P. , Wixom Alexander Q. , Souto Yara , Ladigan-Badura Swetlana , Yonkus Jennifer A. , Abdelrahman Amro M. , Alva-Ruiz Roberto , Gaedcke Jochen , Strobel Philipp , Kosinsky Robyn Laura , Wegwitz Florian , Hermann Patrick , Truty Mark J. , Siveke Jens T. , Hahn Stephan A. , Hessmann Elisabeth , Johnsen Steven A. , Najafova Zeynab
Published: September 2024

Abstract
A major hurdle to the application of precision oncology in pancreatic cancer is the lack of molecular stratification approaches and targeted therapy for defined molecular subtypes. In this work, we sought to gain further insight and identify molecular and epigenetic signatures of the basal-like A pancreatic ductal adenocarcinoma (PDAC) subgroup that can be applied to clinical samples for patient stratification and/or therapy monitoring. We generated and integrated global gene expression and epigenome mapping data from patient-derived xenograft (PDX) models to identify subtype-specific enhancer regions that were validated in patient-derived samples. In addition, complementary nascent transcription and chromatin topology (HiChIP) analyses revealed a basal-like A subtype-specific transcribed enhancer program (B-STEP) in PDAC characterized by enhancer RNA (eRNA) production that is associated with more frequent chromatin interactions and subtype-specific gene activation. Importantly, we successfully confirmed the validity of eRNA detection as a possible histological approach for PDAC patient stratification by performing RNA in situ hybridization analyses for subtype-specific eRNAs on pathological tissue samples. Thus, this study provides proof-of-concept that subtype-specific epigenetic changes relevant for PDAC progression can be detected at a single cell level in complex, heterogeneous, primary tumor material.

Implications: Subtype-specific enhancer activity analysis via detection of eRNAs on a single cell level in patient material can be used as a potential tool for treatment stratification.
Data from HCK promotes high-grade serous ovarian cancer tumorigenesis through CD44 and NOTCH3 signaling
Authors: Khella Christen A. , Franciosa Lucyann , Rodriguez-Rodriguez Lorna , Rajkarnikar Resha , Mythreye Karthikeyan , Gatza Michael L.
Published: September 2024

Abstract
High-grade serous ovarian cancer (HGSOC) is a highly aggressive and lethal subtype of ovarian cancer. While most patients initially respond to standard-of-care treatment, the majority will eventually relapse and succumb to their disease. Despite significant advances in our understanding of this disease, the mechanisms that govern the distinctions between HGSOC with good and poor prognosis remain unclear. In this study, we implemented a proteogenomic approach to analyze gene expression, proteomic and phosphoproteomic proﬁles of HGSOC tumor samples to identify molecular pathways that distinguish HGSOC tumors relative to clinical outcome. Our analyses identify significant upregulation of hematopoietic cell kinase (HCK) expression and signaling in poor prognostic HGSOC patient samples. Analyses of independent gene expression datasets and immunohistochemistry of patient samples confirmed increased HCK signaling in tumors relative to normal fallopian or ovarian samples and demonstrated aberrant expression in tumor epithelial cells. Consistent with the association between HCK expression and tumor aggressiveness in patient samples, in vitro phenotypic studies showed that HCK can, in part, promote cell proliferation, colony formation, and invasive capacity of cell lines. Mechanistically, HCK mediates these phenotypes, partly through CD44 and NOTCH3-dependent signaling, and inhibiting CD44 or NOTCH3 activity, either genetically or through gamma-secretase inhibitors, can revert HCK-driven phenotypes.
Implications: Collectively, these studies establish that HCK acts as an oncogenic driver of HGSOC through aberrant activation of CD44 and NOTCH3 signaling and identifies this network as a potential therapeutic opportunity in a subset of aggressive and recurrent HGSOC patients.
Data from Targeting c-Jun is a potential therapy for luminal breast cancer bone metastasis
Authors: Han Yuxuan , Katayama Shota , Futakuchi Mitsuru , Nakamichi Kazuya , Wakabayashi Yutaro , Sakamoto Mai , Nakayama Jun , Semba Kentaro
Published: September 2024

Abstract
Luminal breast cancer has the highest bone metastasis frequency among all breast cancer subtypes; however, its metastatic mechanism has not been elucidated because of a lack of appropriate models. We have previously developed useful bone metastatic cell lines of luminal breast cancer using MCF7 cells. In this study, we characterized bone metastatic MCF7-BM cell lines and identified c-Jun as a novel bone metastasis marker of luminal breast cancer. The protein level of c-Jun was upregulated in MCF7-BM cells compared with that in parental cells, and its deficiency resulted in the suppression of tumor cell migration, transformation, and reduced osteolytic ability. In vivo, dominant-negative c-Jun exhibited smaller bone metastatic lesions and a lower metastatic frequency. Histological analysis revealed that c-Jun expression was heterogeneous in bone metastatic lesions, whereas c-Jun overexpression mediated a vicious cycle between MCF7-BM cells and osteoclasts by enhancing calcium-induced migration and releasing the osteoclast activator BMP5. Pharmacological inhibition of c-Jun by the Jun amino-terminal kinase (JNK) inhibitor JNK-IN-8 effectively suppressed tumorigenesis and bone metastasis in MCF7-BM cells. Furthermore, c-Jun downstream signals were specifically correlated with the clinical prognosis of patients with the luminal subtype of breast cancer. Our results illustrate the potential benefits of a therapy that targets c-Jun to prevent bone metastasis in luminal breast cancer.

Implications: c-Jun expression mediates bone metastasis in luminal breast cancer by forming a vicious cycle in the bone microenvironment, which reveals potential strategies for subtype-specific bone metastasis therapy.
Data from LncRNA-encoded Micropeptide ACLY‍-‍BP drives lipid deposition and cell proliferation in Clear Cell Renal Cell Carcinoma via maintenance of ACLY acetylation
Authors: Zhang Shenghua , Zhang Zheng , Liu Xiaolong , Deng Yibin , Zheng Jian , Deng Jieqiong , Wang Yirong , Guo Binbin , Li Fanrong , Chen Xiaoyue , Pan Yacheng , Wang Jieyu , Lu Jiachun , Wu Siqi , Guo Qiang , Zhou Yifeng
Published: September 2024

Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of lethal kidney cancer. Reprogramming of fatty acid and glucose metabolism resulting in the accumulation of lipids and glycogen in the cytoplasm is a hallmark of ccRCC. Here, we identified a micropeptide ACLY-BP encoded by the GATA3-suppressed LINC00887, which regulated lipid metabolism and promoted cell proliferation and tumor growth in ccRCC. Mechanistically, the ACLY-BP stabilizes the ATP citrate lyase (ACLY) by maintaining ACLY acetylation and preventing ACLY from ubiquitylation and degradation, thereby leading to lipid deposition in ccRCC and promoting cell proliferation. Our results may offer a new clue for the therapeutic approaches and the diagnostic assessment for ccRCC.
Implications: This study identifies ACLY-BP encoded by LINC00887 as a lipid-related micropeptide that stabilizes ACLY to generate acetyl-CoA, driving lipid deposition and promoting cell proliferation in ccRCC.
Supplementary Table S3 from Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in US Prospective Cohorts
Authors: Lyu Zhangyan , Hang Dong , He Xiaosheng , Wu Kana , Cao Yin , Rosner Bernard , Chan Andrew T. , Ogino Shuji , Li Ni , Dai Min , Giovannucci Edward L. , Song Mingyang
Published: September 2024

Supplementary Table S3: Associations of the included predictors with the risk of high-risk SPs in the NHS and NHS2.
Supplementary Table S2 from Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in US Prospective Cohorts
Authors: Lyu Zhangyan , Hang Dong , He Xiaosheng , Wu Kana , Cao Yin , Rosner Bernard , Chan Andrew T. , Ogino Shuji , Li Ni , Dai Min , Giovannucci Edward L. , Song Mingyang
Published: September 2024

Supplementary Table S2: Associations of the included predictors with the risk of high-risk SPs by sex.
Supplementary Table S1 from Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in US Prospective Cohorts
Authors: Lyu Zhangyan , Hang Dong , He Xiaosheng , Wu Kana , Cao Yin , Rosner Bernard , Chan Andrew T. , Ogino Shuji , Li Ni , Dai Min , Giovannucci Edward L. , Song Mingyang
Published: September 2024

Supplementary Table S1: Characteristics of study participants in the NHS and NHS2 by high-risk SPs.
Supplementary Figure S1 from Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in US Prospective Cohorts
Authors: Lyu Zhangyan , Hang Dong , He Xiaosheng , Wu Kana , Cao Yin , Rosner Bernard , Chan Andrew T. , Ogino Shuji , Li Ni , Dai Min , Giovannucci Edward L. , Song Mingyang
Published: September 2024

Supplementary Figure S1: The flowchart for inclusion and exclusion of study participants in the NHS, NHS2, and HPFS.
Supplementary Table S4 from Validation of an abridged breast cancer risk prediction model for the general population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: September 2024

Supplementary Table S4 shows the expected and observed 5-year risks for each model by decile of risk
Supplementary Table S3 from Validation of an abridged breast cancer risk prediction model for the general population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: September 2024

Supplementary Table S3 shows the characteristics of affected and unaffected participants
Supplementary Table S1 from Validation of an abridged breast cancer risk prediction model for the general population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: September 2024

Supplementary Table S1 shows the relative risks assigned for first-degree family history of breast cancer
Supplementary Methods S1 from Validation of an abridged breast cancer risk prediction model for the general population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: September 2024

Supplementary Methods S1 describes the calculation of the risk scores
Supplementary Figure S1 from Validation of an abridged breast cancer risk prediction model for the general population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: September 2024

Supplementary Figure S1 shows the distributions of the 5-year risks for affected and unaffected women for each model
Supplementary Table S1 from Precision cut lung slices as a preclinical model for non-small cell lung cancer chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clambey Eric T. , Keith Robert L. , Tennis Meredith A.
Published: September 2024

Supplementary Table S1 lists targets in the dot blots for Figures 3D and 4C.
Supplementary Figure S5 from Precision cut lung slices as a preclinical model for non-small cell lung cancer chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clambey Eric T. , Keith Robert L. , Tennis Meredith A.
Published: September 2024

Supplementary Figure S5 shows a representative immunofluorescence image for Figure 5.
Supplementary Figure S1 from Precision cut lung slices as a preclinical model for non-small cell lung cancer chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clambey Eric T. , Keith Robert L. , Tennis Meredith A.
Published: September 2024

Supplementary Figure S1 shows a dot blot for Figure 3D.
Supplemental Table 1 from Breastfeeding and Mammographic Breast Density: A Cross-sectional Study
Authors: Getz Kayla R. , Adedokun Babatunde , Xu Shuai , Toriola Adetunji T.
Published: September 2024

Supplemental Table 1 shows results from IPW analysis.
Supplementary Table S1 from Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma in Situ
Authors: O'Shea Anne E. , Clifton Guy T. , Qiao Na , Heckman-Stoddard Brandy M. , Wojtowicz Malgorzata , Dimond Eileen , Bedrosian Isabelle , Weber Diane , Garber Judy E. , Husband Alexander , Pastorello Ricardo , Lee J. Jack , Hernandez Mike , Liu Diane D. , Vornik Lana A. , Brown Powel H. , Alatrash Gheath , Peoples George E. , Mittendorf Elizabeth A.
Published: September 2024

Supplementary Table S1: Demographics by therapy
Supplementary Fig. S2 from Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma in Situ
Authors: O'Shea Anne E. , Clifton Guy T. , Qiao Na , Heckman-Stoddard Brandy M. , Wojtowicz Malgorzata , Dimond Eileen , Bedrosian Isabelle , Weber Diane , Garber Judy E. , Husband Alexander , Pastorello Ricardo , Lee J. Jack , Hernandez Mike , Liu Diane D. , Vornik Lana A. , Brown Powel H. , Alatrash Gheath , Peoples George E. , Mittendorf Elizabeth A.
Published: September 2024

Supplementary Fig. S2: Nelipepimut-S (NPS)-specific cytotoxic T lymphocyte (CTL) responses in patients receiving GM-CSF alone with corresponding HER2 changes
Supplementary Table 8 from Associations between physical activity and incidence of cancer among overweight adults in Korea: Results from the Health Examinees-G study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: September 2024

Supplementary Table 8 shows the association of physical activity with colorectal cancer incidence
Supplementary Table 7 from Associations between physical activity and incidence of cancer among overweight adults in Korea: Results from the Health Examinees-G study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: September 2024

Supplementary Table 7 shows the association of physical activity with overall cancer incidence in the normal population, defined as those with body mass index between 18.5 and 25.0, after excluding those who were diagnosed with thyroid cancer
Supplementary Table 4 from Associations between physical activity and incidence of cancer among overweight adults in Korea: Results from the Health Examinees-G study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: September 2024

Supplementary Table 4 shows the association of physical activity with overall cancer incidence in participants without a past diagnosis of chronic diseases
Supplementary Table 15 from Associations between physical activity and incidence of cancer among overweight adults in Korea: Results from the Health Examinees-G study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: September 2024

Supplementary Table 15 shows the association of physical activity with prostate cancer incidence
Supplementary Table 14 from Associations between physical activity and incidence of cancer among overweight adults in Korea: Results from the Health Examinees-G study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: September 2024

Supplementary Table 14 shows the association of physical activity with breast cancer incidence stratified by obesity status
Supplementary Table 1 from Associations between physical activity and incidence of cancer among overweight adults in Korea: Results from the Health Examinees-G study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: September 2024

Supplementary Table 1 shows the categorization of physical activity
Supplemental Table 1 from Polymorphisms in the non-homologous end-joining DNA repair pathway are associated with HPV integration in cervical dysplasia
Authors: Geris Jennifer M. , Amirian E. Susan. , Marquez-Do Deborah A. , Guillaud Martial , Dillon Laura M. , Follen Michele , Scheurer Michael E.
Published: September 2024

Supplemental Table 1: Tag SNPs and Calculated Odds Ratios
Supplementary Figure S2 from Progressive spreading of DNA methylation in the GSTP1 promoter CpG island across transitions from precursors to invasive prostate cancer
Authors: Gupta Harshath , Inoue Hitoshi , Nakai Yasutomo , Nakayama Masashi , Jones Tracy , Hicks Jessica L. , Kumar Balasubramanian , Gurel Meltem , Nelson William G. , De Marzo Angelo M. , Yegnasubramanian Srinivasan
Published: September 2024

Supplementary Figure S2 shows the methylation rate by allele of the GSTP1 promoter region for partially methylated PIN alleles and demonstrates a hotspot of methylation around transcription factor binding sites and the transcription start site.
Supplementary Table S6 from Association and prediction utilizing craniocaudal and mediolateral oblique view digital mammography and long-term breast cancer risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: September 2024

Supplementary Table S6: Hazards ratio of association among premenopausal women for baseline risk factors and breast cancer risk utilizing FULL-VPD
Supplementary Table S5 from Association and prediction utilizing craniocaudal and mediolateral oblique view digital mammography and long-term breast cancer risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: September 2024

Supplementary Table S5: Hazards ratio (95% Confidence Interval) for association inure-menopausal women between baseline risk factors and breast cancer risk utilizing MLOL-VPD
Supplementary Table S4 from Association and prediction utilizing craniocaudal and mediolateral oblique view digital mammography and long-term breast cancer risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: September 2024

Supplementary Table S4: Hazards ratio (95% Confidence Interval) for association between baseline risk factors and breast cancer risk among pre-menopausal women using CC-VPD only.
Supplementary Table S2 from Association and prediction utilizing craniocaudal and mediolateral oblique view digital mammography and long-term breast cancer risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: September 2024

Supplementary Table S2: Hazards ratio for association between baseline risk factors and breast cancer risk among postmenopausal women using MLO-VPD only.
Supplementary Figure S1 from Association and prediction utilizing craniocaudal and mediolateral oblique view digital mammography and long-term breast cancer risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: September 2024

Supplementary Figure S1: Cohort recruit and follow up chart.
Supplementary Table 2 from Rates of intervention and cancer detection on initial versus subsequent whole body MRI screening in Li-Fraumeni Syndrome
Authors: Kagami Laura AT. , Du Yun K. , Fernandes Conrad J. , Le Anh N. , Good Madeline , Duvall Melani M. , Baldino Sarah E. , Powers Jacquelyn , Zelley Kristin , States Lisa J. , Mathew Manoj C. , Katona Bryson W. , MacFarland Suzanne P. , Maxwell Kara N.
Published: September 2024

Supplementary Table 2 outlines prior studies of initial WBMRI screening in LFS cohorts both in pediatric and adult patient populations including length of the study, number of patients with findings, and number of cancers detected.
Table S7 from Analysis of several common APOBEC-type mutations in bladder tumors suggests links to viral infection
Authors: Rao Nina , Starrett Gabriel J. , Piaskowski Mary L. , Butler Kelly E. , Golubeva Yelena , Yan Wusheng , Lawrence Scott M. , Dean Michael , Garcia-Closas Montserrat , Baris Dalsu , Johnson Alison , Schwenn Molly , Malats Nuria , Real Francisco X. , Kogevinas Manolis , Rothman Nathaniel , Silverman Debra T. , Dyrskjøt Lars , Buck Christopher B. , Koutros Stella , Prokunina-Olsson Ludmila
Published: September 2024

Table S7: Relationship of PyV status with FGFR3/PIK3CA-mutation status and cigarette smoking
Table S2 from Analysis of several common APOBEC-type mutations in bladder tumors suggests links to viral infection
Authors: Rao Nina , Starrett Gabriel J. , Piaskowski Mary L. , Butler Kelly E. , Golubeva Yelena , Yan Wusheng , Lawrence Scott M. , Dean Michael , Garcia-Closas Montserrat , Baris Dalsu , Johnson Alison , Schwenn Molly , Malats Nuria , Real Francisco X. , Kogevinas Manolis , Rothman Nathaniel , Silverman Debra T. , Dyrskjøt Lars , Buck Christopher B. , Koutros Stella , Prokunina-Olsson Ludmila
Published: September 2024

Table S2: Accession numbers of viruses evaluated in RNA-seq of bladder tumors from UROMOL
Table S1 from Analysis of several common APOBEC-type mutations in bladder tumors suggests links to viral infection
Authors: Rao Nina , Starrett Gabriel J. , Piaskowski Mary L. , Butler Kelly E. , Golubeva Yelena , Yan Wusheng , Lawrence Scott M. , Dean Michael , Garcia-Closas Montserrat , Baris Dalsu , Johnson Alison , Schwenn Molly , Malats Nuria , Real Francisco X. , Kogevinas Manolis , Rothman Nathaniel , Silverman Debra T. , Dyrskjøt Lars , Buck Christopher B. , Koutros Stella , Prokunina-Olsson Ludmila
Published: September 2024

Table S1: Patient summary of demographic characteristics and mutation status in individual sets and the combined BC set
Data from Cost-Effectiveness of p16/Ki-67 Dual-Stained Cytology Reflex Following Co-Testing with hrHPV Genotyping for Cervical Cancer Screening
Authors: Harper Diane M. , Anderson Rye J. , Baker Ed , Yu Tiffany M.
Published: September 2024

Abstract
The first biomarker-based cervical cancer screening test, p16/Ki-67 dual-stained cytology (DS), has been clinically validated and approved in the United States for triage of women being screened for cervical cancer who test positive for high-risk human papillomavirus (hrHPV). The primary aim of this work is to evaluate the cost-effectiveness of DS triage after co-testing findings of positive non-16/18 HPV types and atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) cytology. A payer-perspective Markov microsimulation model was developed to assess the impact of DS reflex testing. Each comparison simulated 12,250 screening-eligible women through health states defined by hrHPV status and genotype, cervical intraepithelial neoplasia (CIN) grades 1-3, invasive cervical cancer (ICC) by stage, and cancer-related or non-cancer death. Screening test performance data were from the IMPACT clinical validation trial. Transition probabilities were from population and natural history studies. Costs of baseline medical care, screening visits, tests, procedures, and ICC were included. DS reflex after co-testing was cost-effective with incremental cost-effectiveness ratios (ICER) per quality-adjusted-life-year (QALY) gained of $15,231 (95% CI $10,717-$25,400) compared to co-testing with hrHPV pooled primary and genotyped reflex testing, and $23,487 (95% CI $15,745-$46,175) compared to co-testing with hrHPV genotyping with no reflex test. Screening and medical costs and life-years increased, while ICC costs and risk of ICC death decreased. Incorporating DS reflex into co-testing cervical cancer screening algorithms is projected to be cost-effective.