ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
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DOI：
10.1016/j.ccell.2016.12.001
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发表时间：
2017-01-09
期刊：
影响因子：
50.3
通讯作者：
Ellisen LW
中科院分区：
文献类型：
--
作者：
Saladi SV;Ross K;Karaayvaz M;Tata PR;Mou H;Rajagopal J;Ramaswamy S;Ellisen LW
在许多癌症中观察到SWI/SNF染色质重塑亚基基因的功能丧失突变，但SWI/SNF的致癌作用尚未完全确定。在这里，我们发现，ACTL 6A，编码SWI/SNF亚基连接到干细胞和祖细胞的功能，经常共同扩增和高度表达的p53家族成员p63在头颈部鳞状细胞癌（HNSCC）。ACTL 6A和p63物理相互作用，协同控制促进增殖和抑制分化的转录程序，部分通过包括WWC 1在内的调节因子激活Hippo-YAP途径。异位ACTL 6A/p63表达促进肿瘤发生，而ACTL 6A表达和雅普激活在原发性HNSCC中高度相关，并预测患者生存率差。因此，ACTL 6A和p63在HNSCC中协同作为致癌驱动因子。
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.