Actin like-6A promotes glioma progression through stabilization of transcriptional regulators YAP/TAZ.
Actin like-6A promotes glioma progression through stabilization of transcriptional regulators YAP/TAZ.
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Actin like-6A 通过稳定转录调节因子 YAP/TAZ 促进神经胶质瘤进展。
DOI：
10.1038/s41419-018-0548-3
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发表时间：
2018-05-01
影响因子：
9
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Ji J;Xu R;Zhang X;Han M;Xu Y;Wei Y;Ding K;Wang S;Bin Huang;Chen A;Di Zhang;Jiang Z;Xu S;Zhang Q;Li W;Ni S;Wang J;Li X
增加的肌动蛋白样6A（ACTL 6A）表达与多种癌症的发展有关，并且最近与Hippo信号传导通路相关，已知Hippo信号传导通路调节生物学特性，包括增殖、组织再生、干细胞生物学以及肿瘤发生。在这里，我们首先表明，ACTL 6A是上调的人胶质瘤和它的表达与胶质瘤患者的生存。ACTL 6A在体外和原位异种移植模型中促进胶质瘤细胞的恶性行为。在免疫共沉淀实验中，我们发现ACTL 6A与雅普/TAZ物理结合，并进一步破坏了雅普与β-TrCP E3泛素连接酶之间的相互作用，从而促进了雅普蛋白的降解。此外，ACTL 6A对胶质瘤细胞增殖、迁移和侵袭的影响可通过雅普/TAZ介导。这些数据表明，ACTL 6A可能通过稳定雅普/TAZ而促进癌症进展，因此为治疗人神经胶质瘤提供了新的治疗靶点。
Increased Actin-like 6A (ACTL6A) expression has been implicated in the development of diverse cancers and recently associated with the Hippo signaling pathway, which is known to regulate biological properties, including proliferation, tissue regeneration, stem cell biology, as well as tumorigenesis. Here we first show that ACTL6A is upregulated in human gliomas and its expression is associated with glioma patient survival. ACTL6A promotes malignant behaviors of glioma cells in vitro and in orthotopic xenograft model. In co-immunoprecipitation assays, we discover that ACTL6A physically associated with YAP/TAZ and furthermore disrupts the interaction between YAP and β-TrCP E3 ubiquitin ligase, which promotes YAP protein degradation. Moreover, effects of ACTL6A on glioma cells proliferation, migration, and invasion could be mediated by YAP/TAZ. These data indicate that ACTL6A may contribute to cancer progression by stabilizing YAP/TAZ and therefore provide a novel therapeutic target for the treatment of human gliomas.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
影响因子：
8
作者：
Ehsanian, R.;Brown, M.;Lu, H.;Yang, X. P.;Pattatheyil, A.;Yan, B.;Duggal, P.;Chuang, R.;Doondeea, J.;Feller, S.;Sudol, M.;Chen, Z.;Van Waes, C.
通讯作者：
Van Waes, C.
影响因子：
4.8
作者：
Hiemer, Samantha E.;Szymaniak, Aleksander D.;Varelas, Xaralabos
通讯作者：
Varelas, Xaralabos
影响因子：
--
作者：
Li W;Dong S;Wei W;Wang G;Zhang A;Pu P;Jia Z
通讯作者：
Jia Z
影响因子：
50.3
作者：
Saladi SV;Ross K;Karaayvaz M;Tata PR;Mou H;Rajagopal J;Ramaswamy S;Ellisen LW
通讯作者：
Ellisen LW