Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity.

ABSTRACT: Cancer heterogeneity impacts therapeutic response, driving efforts to discover over-arching rules that supersede variability. Here, we define pan-cancer binary classes based on distinct expression of YAP and YAP-responsive adhesion regulators. Combining informatics with in vivo and in vitro gain- and loss-of-function studies across multiple murine and human tumor types, we show that opposite pro- or anti-cancer YAP activity functionally defines binary YAP^on or YAP^off cancer classes that express or silence YAP, respectively. YAP^off solid cancers are neural/neuroendocrine and frequently RB1^-/-, such as retinoblastoma, small cell lung cancer, and neuroendocrine prostate cancer. YAP silencing is intrinsic to the cell of origin, or acquired with linea

SUBMITTER: Pearson JD 

PROVIDER: S-EPMC8981970 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature