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

Autor:	Maxfield KE; Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas, Texas 75390, USA., Taus PJ; Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas, Texas 75390, USA.; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA., Corcoran K; Department of Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA., Wooten J; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA., Macion J; Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas, Texas 75390, USA., Zhou Y; Department of Clinical Science, UT-Southwestern Medical Center, Dallas, Texas 75390, USA., Borromeo M; Department of Neuroscience, UT-Southwestern Medical Center, Dallas, Texas 75390, USA., Kollipara RK; Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA., Yan J; Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas, Texas 75390, USA., Xie Y; Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas, Texas 75390, USA.; Department of Clinical Science, UT-Southwestern Medical Center, Dallas, Texas 75390, USA., Xie XJ; Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas, Texas 75390, USA.; Department of Clinical Science, UT-Southwestern Medical Center, Dallas, Texas 75390, USA., Whitehurst AW; Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas, Texas 75390, USA.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2015 Nov 16; Vol. 6, pp. 8840. Date of Electronic Publication: 2015 Nov 16.
DOI:	10.1038/ncomms9840
Abstrakt:	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.
Databáze:	MEDLINE
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