Research progress on the regulatory mechanisms of FOXC1 expression in cancers and its role in drug resistance

Gene. 2024 Mar 1:897:148079. doi: 10.1016/j.gene.2023.148079. Epub 2023 Dec 13.

Abstract

The Forkhead box C1 (FOXC1) transcription factor is an important member of the FOX family. After initially being identified in triple-negative breast cancer (TNBC) with significant oncogenic function, FOXC1 was subsequently demonstrated to be involved in the development of more than 16 types of cancers. In recent years, increasing studies have focused on the deregulatory mechanisms of FOXC1 expression and revealed that FOXC1 expression was regulated at multiple levels including transcriptional regulation, post-transcription regulation and post-translational modification. Moreover, dysregulation of FOXC1 is also implicated in drug resistance in various types of cancer, especially in breast cancer, which further emphasizes the translational and clinical significance of FOXC1 as a therapeutic target in cancer treatment. This review summarizes recent findings on mechanisms of FOXC1 dysregulation in cancers and its role in chemoresistance, which will help to better understand the oncogenic role of FOXC1, overcome FOXC1-mediated drug resistance and develop targeted therapy for FOXC1 in cancers.

Keywords: Cancer; Drug resistance; Epigenetic regulation; FOXC1; Post-translational modification; Transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Cell Line, Tumor
  • Drug Resistance, Neoplasm*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Triple Negative Breast Neoplasms* / genetics

Substances

  • Forkhead Transcription Factors
  • FOXC1 protein, human