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

Int J Biol Sci. 2025 Jan 1;21(2):758-771. doi: 10.7150/ijbs.105265. eCollection 2025.

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.

Keywords: FKBP10; lamin A; muscle-invasive bladder cancer; nuclear atypia; prelamin A.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Lamin Type A* / genetics
  • Lamin Type A* / metabolism
  • Male
  • Mice
  • Neoplasm Invasiveness
  • Tacrolimus Binding Proteins* / genetics
  • Tacrolimus Binding Proteins* / metabolism
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Tacrolimus Binding Proteins
  • Lamin Type A
  • FKBP10 protein, human