CHFR‑mediated epithelial‑to‑mesenchymal transition promotes metastasis in human breast cancer cells

Mol Med Rep. 2021 Jun;23(6):451. doi: 10.3892/mmr.2021.12090. Epub 2021 Apr 21.

Abstract

Checkpoint with FHA and RING finger domains (CHFR) is a G2 phase/mitosis checkpoint. Several studies have reported that CHFR is downregulated in multiple cancer types and serves a tumor suppressor role. However, the biological function of CHFR in breast cancer (BRCA), particularly regarding metastasis, are yet to be elucidated. In the present study, it was revealed that CHFR is upregulated in BRCA compared with normal tissues, according to The Cancer Genome Atlas database. In addition, subgroup analysis of BRCA revealed that CHFR was upregulated in both human epidermal growth factor receptor 2‑positive and triple‑negative BRCA. Meanwhile, patients with high expression levels of CHFR exhibited poorer overall survival rates. Furthermore, the present data revealed that the overexpression of CHFR in SKBR3 cells resulted in enhanced cell migration and invasiveness, and also significantly upregulated mesenchymal markers, such as N‑cadherin, vimentin, transcription factor Slug and tight junction protein claudin‑1. Furthermore, knockdown of CHFR in MDA‑MB‑231 cells significantly inhibited cell migration and invasiveness, and also downregulated mesenchymal markers, such as N‑cadherin, vimentin and tight junction protein claudin‑1. In conclusion, the current results indicated that CHFR expression was associated with cell metastasis in BRCA by mediating epithelial‑to‑mesenchymal transition.

Keywords: breast cancer; checkpoint with FHA and RING finger domains; epithelial‑to‑mesenchymal transition; metastasis.

MeSH terms

  • Breast Neoplasms
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Mitosis
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • Triple Negative Breast Neoplasms
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Poly-ADP-Ribose Binding Proteins
  • CHFR protein, human
  • Ubiquitin-Protein Ligases