ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.

Journal Article (Journal Article)

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 an SWI/SNF subunit linked to stem cell 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.

Full Text

Duke Authors

Cited Authors

  • Saladi, SV; Ross, K; Karaayvaz, M; Tata, PR; Mou, H; Rajagopal, J; Ramaswamy, S; Ellisen, LW

Published Date

  • January 9, 2017

Published In

Volume / Issue

  • 31 / 1

Start / End Page

  • 35 - 49

PubMed ID

  • 28041841

Pubmed Central ID

  • PMC5225026

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2016.12.001


  • eng

Conference Location

  • United States