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      ACTL6A is co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation and Poor Prognosis

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          SUMMARY

          Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact, cooperatively controlling a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Ectopic ACTL6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC.

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          Author and article information

          Journal
          101130617
          29778
          Cancer Cell
          Cancer Cell
          Cancer cell
          1535-6108
          1878-3686
          20 December 2016
          29 December 2016
          09 January 2017
          09 January 2018
          : 31
          : 1
          : 35-49
          Affiliations
          [1 ]Massachusetts General Hospital Cancer Center, Boston, MA 02114
          [2 ]Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114
          [3 ]Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA 02114
          [4 ]Harvard Stem Cell Institute, Cambridge, MA 02138, USA
          [5 ]Harvard Medical School, Boston, MA 02115
          [6 ]Broad Institute of MIT and Harvard, Cambridge, MA 02138
          Author notes
          [¶]

          Current Address: Department of Cell Biology, Duke University School of Medicine Durham, NC 27516

          [* ]Correspondence: Leif W. Ellisen, M.D., Ph.D., MGH Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, lellisen@ 123456mgh.harvard.edu
          Article
          PMC5225026 PMC5225026 5225026 nihpa835049
          10.1016/j.ccell.2016.12.001
          5225026
          28041841
          78ff0afa-e66d-4de5-8ec2-12f9e5244356
          History
          Categories
          Article

          HNSCC,squamous cell carcinoma,p63,SWI/SNF (BAF) complex,chromatin remodeling,Hippo pathway

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