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Cancer Cell. 2017 Jan 9;31(1):35-49. doi: 10.1016/j.ccell.2016.12.001. Epub 2016 Dec 29.

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

Author information

1
Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
2
Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA.
3
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02115, USA.
4
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02115, USA.
5
Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA.
6
Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: lellisen@mgh.harvard.edu.

Abstract

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.

KEYWORDS:

ACTL6A; HNSCC; SWI/SNF (BAF) complex; YAP1; chromatin remodeling; hippo pathway; p63; squamous cell carcinoma

PMID:
28041841
PMCID:
PMC5225026
DOI:
10.1016/j.ccell.2016.12.001
[Indexed for MEDLINE]
Free PMC Article

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