Key Laboratory of Brain Functional Remodeling, Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, 250012, China.
Brain and Mind Centre, and Faculty of Health Sciences, University of Sydney, Camperdown, NSW 2050, Australia.
Cell Death Dis. 2018 May 1;9(5):517. doi: 10.1038/s41419-018-0548-3.
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.
肌动蛋白样蛋白 6A（ACTL6A）的表达增加与多种癌症的发生有关，最近与 Hippo 信号通路有关，该通路已知可调节包括增殖、组织再生、干细胞生物学以及肿瘤发生在内的生物学特性。在这里，我们首先表明 ACTL6A 在人类神经胶质瘤中上调，其表达与神经胶质瘤患者的生存有关。ACTL6A 在体外和原位异种移植模型中促进神经胶质瘤细胞的恶性行为。在共免疫沉淀测定中，我们发现 ACTL6A 与 YAP/TAZ 物理结合，并且进一步破坏 YAP 与 β-TrCP E3 泛素连接酶之间的相互作用，从而促进 YAP 蛋白降解。此外，ACTL6A 对神经胶质瘤细胞增殖、迁移和侵袭的影响可以通过 YAP/TAZ 介导。这些数据表明，ACTL6A 通过稳定 YAP/TAZ 可能有助于癌症进展，因此为治疗人类神经胶质瘤提供了一个新的治疗靶点。
