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 and Angelique W. Whitehurst ()
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Kimberly E. Maxfield: Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center
Patrick J. Taus: Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center
Kathleen Corcoran: University of North Carolina at Chapel Hill
Joshua Wooten: University of North Carolina at Chapel Hill
Jennifer Macion: Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center
Yunyun Zhou: UT-Southwestern Medical Center
Mark Borromeo: UT-Southwestern Medical Center
Rahul K. Kollipara: Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center
Jingsheng Yan: Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center
Yang Xie: Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center
Xian-Jin Xie: Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center
Angelique W. Whitehurst: Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9840

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