Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer

Kimberly E. Maxfield, Patrick J. Taus, Kathleen Corcoran, Joshua Wooten, Jennifer MacIon, Yunyun Zhou, Mark Borromeo, Rahul K. Kollipara, Jingsheng Yan, Yang Xie, Xian Jin Xie, Angelique W. Whitehurst

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology.

Original languageEnglish (US)
Article number8840
JournalNature Communications
Volume6
DOIs
StatePublished - Nov 16 2015

Fingerprint

testes
Testicular Neoplasms
antigens
cancer
Testis
Antigens
Tumors
Neoplasms
Cells
Triple Negative Breast Neoplasms
tumors
Poisons
viability
Neoplasm Antigens
Genomics
Gene expression
Assays
Cell Survival
negative feedback
Feedback

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer. / Maxfield, Kimberly E.; Taus, Patrick J.; Corcoran, Kathleen; Wooten, Joshua; MacIon, Jennifer; Zhou, Yunyun; Borromeo, Mark; Kollipara, Rahul K.; Yan, Jingsheng; Xie, Yang; Xie, Xian Jin; Whitehurst, Angelique W.

In: Nature Communications, Vol. 6, 8840, 16.11.2015.

Research output: Contribution to journalArticle

Maxfield, Kimberly E. ; Taus, Patrick J. ; Corcoran, Kathleen ; Wooten, Joshua ; MacIon, Jennifer ; Zhou, Yunyun ; Borromeo, Mark ; Kollipara, Rahul K. ; Yan, Jingsheng ; Xie, Yang ; Xie, Xian Jin ; Whitehurst, Angelique W. / Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer. In: Nature Communications. 2015 ; Vol. 6.
@article{b0092d502f8a490ea2c56bc019cca9b8,
title = "Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer",
abstract = "Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology.",
author = "Maxfield, {Kimberly E.} and Taus, {Patrick J.} and Kathleen Corcoran and Joshua Wooten and Jennifer MacIon and Yunyun Zhou and Mark Borromeo and Kollipara, {Rahul K.} and Jingsheng Yan and Yang Xie and Xie, {Xian Jin} and Whitehurst, {Angelique W.}",
year = "2015",
month = "11",
day = "16",
doi = "10.1038/ncomms9840",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer

AU - Maxfield, Kimberly E.

AU - Taus, Patrick J.

AU - Corcoran, Kathleen

AU - Wooten, Joshua

AU - MacIon, Jennifer

AU - Zhou, Yunyun

AU - Borromeo, Mark

AU - Kollipara, Rahul K.

AU - Yan, Jingsheng

AU - Xie, Yang

AU - Xie, Xian Jin

AU - Whitehurst, Angelique W.

PY - 2015/11/16

Y1 - 2015/11/16

N2 - Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology.

AB - Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology.

UR - http://www.scopus.com/inward/record.url?scp=84947294079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947294079&partnerID=8YFLogxK

U2 - 10.1038/ncomms9840

DO - 10.1038/ncomms9840

M3 - Article

C2 - 26567849

AN - SCOPUS:84947294079

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8840

ER -