Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Pingjiang Road 23, Hexi District, Tianjin, 300211, China.
Department of Urology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, 453100, China.
Exp Cell Res. 2020 May 15;390(2):111952. doi: 10.1016/j.yexcr.2020.111952. Epub 2020 Mar 7.
Although primary cilia abnormalities have been frequently observed in multiple cancers, including prostate cancer (PCa), the molecular mechanisms underlying primary ciliogenesis repression in PCa cells remain unclear. Transforming acidic coiled-coil protein-3 (TACC3), whose deregulation has been implicated in the pathogenesis of several types of cancer, is a key centrosomal protein that plays a crucial role in centrosome/microtubule dynamics, potentially impacting primary cilium generation. Here, we showed that TACC3 was markedly upregulated in PCa and that knockdown of TACC3 restrained tumorigenesis and tumor growth in vitro and in vivo. Additionally, we found that TACC3 interacts with filamin A, and elevated levels of TACC3 disrupted the interaction between filamin A and meckelin, thereby restraining primary cilium formation in PCa cells.
虽然初级纤毛异常在多种癌症中经常被观察到，包括前列腺癌（PCa），但 PCa 细胞中初级纤毛发生抑制的分子机制尚不清楚。转化酸性卷曲螺旋蛋白-3（TACC3）的失调与多种类型癌症的发病机制有关，是一种关键的中心体蛋白，在中心体/微管动力学中发挥着重要作用，可能影响初级纤毛的产生。在这里，我们发现 TACC3 在 PCa 中明显上调，并且敲低 TACC3 抑制了体外和体内的肿瘤发生和肿瘤生长。此外，我们发现 TACC3 与细丝蛋白 A 相互作用，并且 TACC3 水平的升高破坏了细丝蛋白 A 与 Meckelin 之间的相互作用，从而抑制了 PCa 细胞中初级纤毛的形成。
