FOXM1 facilitates breast cancer cell stemness and migration in YAP1-dependent manner

Arch Biochem Biophys. 2020 May 30:685:108349. doi: 10.1016/j.abb.2020.108349. Epub 2020 Mar 21.

Abstract

Breast cancer has the highest incidence and mortality in the female population. Forkhead box M1 (FOXM1) known as a transcription factor is upregulated and associated with poor prognosis in a variety of cancers. However, the molecular mechanisms of FOXM1 on breast cancer progression are poorly understood. In this study, we found that FOXM1 was up-regulated in breast cancer. FOXM1 promoted cell proliferation, clonal formation, and migration capacity in triple negative breast cancer by increasing transcriptional activity of YAP1. FOXM1 also maintained cell stemness via the Hippo pathway. The YAP1-TEAD binding inhibitor Verteporfin reduced the transcription level of OCT4 and NANOG but the Hippo pathway activator XMU-MP-1 could increase the transcription level of OCT4 and NANOG. In summary, our findings indicated that FOXM1 promoted breast cancer progression through the Hippo pathway, and it was suggested a new strategy to treat breast cancer.

Keywords: Breast cancer; Cancer stemness; FOXM1; YAP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Biomarkers / metabolism
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Forkhead Box Protein M1 / genetics
  • Forkhead Box Protein M1 / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Nanog Homeobox Protein / metabolism
  • Neoplastic Stem Cells / metabolism*
  • Octamer Transcription Factor-3 / metabolism
  • Phosphorylation / genetics
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Up-Regulation
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human