» Articles » PMID: 39781460

FKBP10 Promotes the Muscle Invasion of Bladder Cancer Via Lamin A Dysregulation

Overview
Journal Int J Biol Sci
Date 2025 Jan 9
PMID 39781460
Authors
Affiliations
Soon will be listed here.
Abstract

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.

References
1.
Forlino A, Cabral W, Barnes A, Marini J . New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 2011; 7(9):540-57. PMC: 3443407. DOI: 10.1038/nrendo.2011.81. View

2.
Cho S, Irianto J, Discher D . Mechanosensing by the nucleus: From pathways to scaling relationships. J Cell Biol. 2017; 216(2):305-315. PMC: 5294790. DOI: 10.1083/jcb.201610042. View

3.
Jun T, Hahn N, Sonpavde G, Albany C, MacVicar G, Hauke R . Phase II Clinical and Translational Study of Everolimus ± Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma. Oncologist. 2022; 27(6):432-e452. PMC: 9177111. DOI: 10.1093/oncolo/oyab075. View

4.
Klorin G, Halachmi S, Nativ O, Massalha Y, Stroller L, Amit A . Morphometric analysis of nuclear symmetry in urothelial carcinoma for predicting tumor recurrence. Microsc Res Tech. 2021; 84(11):2559-2564. DOI: 10.1002/jemt.23805. View

5.
Bertacchini J, Beretti F, Cenni V, Guida M, Gibellini F, Mediani L . The protein kinase Akt/PKB regulates both prelamin A degradation and Lmna gene expression. FASEB J. 2013; 27(6):2145-55. DOI: 10.1096/fj.12-218214. View