在鳞状细胞癌中，ACTL6A与p63共同扩增以驱动YAP激活、再生性增殖和不良预后。
ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
作者信息
Saladi Srinivas Vinod, Ross Kenneth, Karaayvaz Mihriban, Tata Purushothama R, Mou Hongmei, Rajagopal Jayaraj, Ramaswamy Sridhar, Ellisen Leif W
机构信息
Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Massachusetts General Hospital Cancer Center, GRJ-904, 55 Fruit Street, Boston, MA 02114, USA.
出版信息
Cancer Cell. 2017 Jan 9;31(1):35-49. doi: 10.1016/j.ccell.2016.12.001. Epub 2016 Dec 29.
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.
摘要
在许多癌症中都观察到SWI/SNF染色质重塑亚基基因的功能丧失突变，但SWI/SNF的致癌作用尚未明确确立。在此，我们发现，编码与干细胞和祖细胞功能相关的SWI/SNF亚基的ACTL6A，在头颈部鳞状细胞癌（HNSCC）中经常与p53家族成员p63共同扩增并高表达。ACTL6A和p63发生物理相互作用，协同控制一个促进增殖和抑制分化的转录程序，部分是通过包括WWC1在内的调节因子激活Hippo-YAP通路。异位表达ACTL6A/p63可促进肿瘤发生，而ACTL6A的表达与YAP的激活在原发性HNSCC中高度相关，并预示患者生存不良。因此，ACTL6A和p63在HNSCC中作为致癌驱动因子协同作用。
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