Zhao Xupeng, Wang Jichen, Tian Shuo, Tang Lu, Cao Shouqing, Ye Jiali, Cai Tianwei, Xuan Yundong, Zhang Xu, Li Xiubin, Li Hongzhao
School of Medicine, Nankai University, Tianjin, China.
Department of Urology, Chinese PLA General Hospital, Beijing, China.
Int J Biol Sci. 2025 Jan 1;21(2):758-771. doi: 10.7150/ijbs.105265. eCollection 2025.
Bladder cancer (BC) is a prevalent urinary malignancy and muscle-invasive bladder cancer (MIBC) is particularly aggressive and associated with poor prognosis. One of MIBC features is the nuclear atypia. However, the molecular mechanism underlying MIBC remains unclear. Here, we find that FKBP10 is significantly upregulated in MIBC tissues and correlated with metastasis and poor outcomes. FKBP10 promotes tumor cell invasion, migration, and metastasis, but not proliferation. Notably, FKBP10 enhances the nuclear atypia of BC cells. Mechanistically, FKBP10 interacts with prelamin A and hinder the nuclear entry of prelamin A, thereby leading to the decrease in the nuclear lamin A, a key factor involved in nuclear atypia. In human BC tissues, nuclear lamin A is downregulated and negatively correlated with FKBP10 expression. Overall, our findings demonstrate that the FKBP10/prelamin A/lamin A axis contributes to MIBC.
膀胱癌(BC)是一种常见的泌尿系统恶性肿瘤,肌层浸润性膀胱癌(MIBC)尤其具有侵袭性,且预后较差。MIBC的特征之一是核异型性。然而,MIBC潜在的分子机制仍不清楚。在此,我们发现FKBP10在MIBC组织中显著上调,并与转移和不良预后相关。FKBP10促进肿瘤细胞侵袭、迁移和转移,但不促进增殖。值得注意的是,FKBP10增强了膀胱癌细胞的核异型性。从机制上讲,FKBP10与前体核纤层蛋白A相互作用,阻碍前体核纤层蛋白A进入细胞核,从而导致核纤层蛋白A减少,而核纤层蛋白A是参与核异型性的关键因素。在人类BC组织中,核纤层蛋白A下调,且与FKBP10表达呈负相关。总体而言,我们的研究结果表明FKBP10/前体核纤层蛋白A/核纤层蛋白A轴促成了MIBC。