YAP1 and PRDM14 converge to promote cell survival and tumorigenesis.

Autor:	Kim M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Ly SH; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Xie Y; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Duronio GN; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Ford-Roshon D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Hwang JH; Masonic Cancer Center and Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA., Sulahian R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Rennhack JP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., So J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Gjoerup O; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Talamas JA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Grandclaudon M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Long HW; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Doench JG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Sethi NS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Giannakis M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Hahn WC; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: william_hahn@dfci.harvard.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2022 Jan 24; Vol. 57 (2), pp. 212-227.e8. Date of Electronic Publication: 2022 Jan 05.
DOI:	10.1016/j.devcel.2021.12.006
Abstrakt:	The transcriptional co-activator YAP1 oncogene is the downstream effector of the Hippo pathway, which regulates tissue homeostasis, organ size, regeneration, and tumorigenesis. Multiple cancers are dependent on sustained expression of YAP1 for cell proliferation, survival, and tumorigenesis, but the molecular basis of this oncogene dependency is not well understood. To identify genes that can functionally substitute for YAP1, we performed a genome-scale genetic rescue screen in YAP1-dependent colon cancer cells expressing an inducible YAP1-specific shRNA. We found that the transcription factor PRDM14 rescued cell proliferation and tumorigenesis upon YAP1 suppression in YAP1-dependent cells, xenografts, and colon cancer organoids. YAP1 and PRDM14 individually activated the transcription of calmodulin 2 (CALM2) and a glucose transporter SLC2A1 upon YAP1 suppression, and CALM2 or SLC2A1 expression was required for the rescue of YAP1 suppression. Together, these findings implicate PRDM14-mediated transcriptional upregulation of CALM2 and SLC2A1 as key components of oncogenic YAP1 signaling and dependency. Competing Interests: Declaration of interests W.C.H. is a consultant for Thermo Fisher, Solasta Ventures, MPM Capital, KSQ Therapeutics, iTeos, Tyra Biosciences, Frontier Medicine, Jubilant Therapeutics, RAPPTA Therapeutics, Function Oncology, and Calyx. M.G. receives research funding from Bristol-Myers-Squibb, Merck, Servier, and Janssen. J.H.H. is a consultant for Astrin Biosciences, Principal Investigator for Caris Life Sciences Genitourinary disease working group. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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