Zhaojie Lyu, Yuchen Liu, Miao Chen, Yacun Chen, Shayi Wu, Anbang He, Xinhui Liao, Meng Zhang, Peipei Wu, Hongbing Mei, Feng Wang, Zhiming Cai, Xinyuan Guan
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China Department of Urology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
Key Laboratory of Medical Reprogramming Technology, Department of Urology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Ther Adv Med Oncol. 2019 Apr 29;11:1758835919841235. doi: 10.1177/1758835919841235. eCollection 2019.
Transitional cell carcinoma (TCC) of the bladder, the major histologic subtype of bladder cancer, is increasing in incidence and mortality, which requires the identification of effective biomarkers. Actin-regulating proteins have recently been proposed as important antitumor druggable targets. As a gelsolin-family actin-modulating protein, CAPG (gelsolin-like actin-capping protein) generated great interest due to its crucial effects in various biological and physiological processes; however, the role and mechanism of CAPG in TCCs remain unknown.
Bioinformatic analysis and immunohistochemistry of clinical specimens were performed to detect the expression level of CAPG. Both and assays were used to determine the oncogenic effect of CAPG in TCCs. Male 4-5-week-old BALB/c nude mice were used for tumorigenesis assays, while SCID mice were used for metastatic assays. Affymetrix microarray was used to identify the underlying molecular mechanism. Western blot and immunofluorescence were used to validate the expression and localization of proteins.
CAPG was frequently upregulated in TCCs and associated with clinical aggressiveness and worse prognosis. Functional assays demonstrated that CAPG could contribute to the tumorigenesis, metastasis and epithelial-mesenchymal transition (EMT) of TCCs both and . A novel mechanism that CAPG promoted TCC development inactivating the Hippo pathway, leading to a nucleus translocation of Yes-associated protein was suggested.
The current study identified CAPG as a novel and critical oncogene in TCCs, supporting the pursuit of CAPG as a potential target for TCC intervention.
膀胱移行细胞癌（TCC）是膀胱癌的主要组织学亚型，其发病率和死亡率正在上升，这需要鉴定有效的生物标志物。肌动蛋白调节蛋白最近被认为是重要的可靶向抗肿瘤药物靶点。作为凝溶胶蛋白家族的肌动蛋白调节蛋白，CAPG（凝溶胶蛋白样肌动蛋白封端蛋白）因其在各种生物学和生理过程中的关键作用而备受关注；然而，CAPG在TCC中的作用和机制仍不清楚。
对临床标本进行生物信息学分析和免疫组织化学检测CAPG的表达水平。采用细胞实验和动物实验确定CAPG在TCC中的致癌作用。4至5周龄的雄性BALB/c裸鼠用于肿瘤发生实验，而SCID小鼠用于转移实验。使用Affymetrix微阵列鉴定潜在的分子机制。蛋白质印迹法和免疫荧光法用于验证蛋白质的表达和定位。
CAPG在TCC中经常上调，并与临床侵袭性和较差的预后相关。功能实验表明，CAPG在体内和体外均可促进TCC的肿瘤发生、转移和上皮-间质转化（EMT）。提出了一种新机制，即CAPG通过失活Hippo通路促进TCC发展，导致Yes相关蛋白的核转位。
本研究确定CAPG是TCC中的一种新的关键致癌基因，支持将CAPG作为TCC干预的潜在靶点进行研究。
