title: ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
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.
authors.affiliation: Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Srinivas Vinod
authors.initials: SV
authors.lastname: Saladi
authors.affiliation: Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ross
authors.affiliation: Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mihriban
authors.initials: M
authors.lastname: Karaayvaz
authors.affiliation: 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.
authors.forename: Purushothama R
authors.initials: PR
authors.lastname: Tata
authors.affiliation: 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.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mou
authors.affiliation: 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.
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Rajagopal
authors.affiliation: 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.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Ramaswamy
authors.affiliation: 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.
authors.forename: Leif W
authors.initials: LW
authors.lastname: Ellisen
mesh_terms: D000199:Actins / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000401:mortality; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000209:etiology* / Q000401:mortality; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D010750:Phosphoproteins / Q000502:physiology*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors; D059467:Transcriptome; D000091102:YAP-Signaling Proteins
chemical_list: C116160:ACTL6A protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C081876:CKAP4 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C513637:WWC1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: ACTL6A; HNSCC; SWI/SNF (BAF) complex; YAP1; chromatin remodeling; hippo pathway; p63; squamous cell carcinoma