Takai Yuki, Naito Sei, Ito Hiromi, Horie Shigemitsu, Ushijima Masaki, Narisawa Takafumi, Yagi Mayu, Ichiyanagi Osamu, Tsuchiya Norihiko
Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Int J Mol Sci. 2025 Apr 29;26(9):4232. doi: 10.3390/ijms26094232.
Ankyrin repeat domain 1 (Ankrd1), a transcriptional target of Yes-associated protein (YAP), is linked to cardiomyopathy. However, its role in cancer, particularly in clear cell renal cell carcinoma (ccRCC), remains vague. In this study, we examined the expression, regulation, and function of Ankrd1 in ccRCC. High Ankrd1 expression was related to poor prognosis in patients with ccRCC in The Cancer Genome Atlas cohort. Ankrd1 expression was regulated by YAP in all ccRCC cell lines examined and also by ERK5 in a subset of ccRCC cell lines. Moreover, silencing of Ankrd1 in ccRCC cell lines resulted in decreased cell motility, whereas its overexpression increased the cell motility. Ankrd1 colocalized with F-actin in lamellipodia upon phorbol ester stimulation. Ankrd1 silencing resulted in alterations in the shape of RCC cells and caused a decrease in lamellipodia formation. Ankrd1 also colocalized with talin-1 in lamellipodia. Ankrd1 depletion repressed talin-1-mediated activation of the integrin pathway. Immunohistochemical examination of surgical specimens revealed high expression of Ankrd1 in metastatic RCC tissues compared with that in primary RCC tissues from the same patients. Collectively, these findings suggest that Ankrd1 plays a critical role in the motility of ccRCC cells through lamellipodia formation.
锚蛋白重复结构域1（Ankrd1）是Yes相关蛋白（YAP）的转录靶点，与心肌病有关。然而，其在癌症中的作用，尤其是在透明细胞肾细胞癌（ccRCC）中的作用仍不明确。在本研究中，我们检测了Ankrd1在ccRCC中的表达、调控及其功能。在癌症基因组图谱队列中，Ankrd1高表达与ccRCC患者的不良预后相关。在所检测的所有ccRCC细胞系中，Ankrd1的表达受YAP调控，在一部分ccRCC细胞系中还受ERK5调控。此外，在ccRCC细胞系中沉默Ankrd1会导致细胞运动性降低，而其过表达则会增加细胞运动性。在佛波酯刺激下，Ankrd1在板状伪足中与F-肌动蛋白共定位。Ankrd1沉默导致RCC细胞形态改变，并使板状伪足形成减少。Ankrd1在板状伪足中也与踝蛋白-1共定位。Ankrd1缺失抑制了踝蛋白-1介导的整合素途径激活。手术标本的免疫组织化学检查显示，与同一患者的原发性RCC组织相比，转移性RCC组织中Ankrd1高表达。总的来说，这些发现表明Ankrd1通过板状伪足形成在ccRCC细胞的运动中起关键作用。
