Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway

Oncogene. 2018 Jul;37(30):4137-4150. doi: 10.1038/s41388-018-0253-9. Epub 2018 Apr 30.

Abstract

The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients. We found that GAS7 was associated with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis via blocking CYFIP1 and Rac1 protein interaction, actin polymerization, and β1-integrin/FAK/Src signaling. We further demonstrated that p53 directly regulated GAS7 gene expression, which was inversely correlated with p53 mutations in breast cancer specimens. Our study uncover a novel regulatory mechanism of p53 in early onset breast cancer progression through GAS7-CYFIP1-mediated signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Female
  • Focal Adhesion Kinase 1 / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Integrin beta1 / genetics
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • MCF-7 Cells
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Signal Transduction / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Up-Regulation / genetics*
  • Wiskott-Aldrich Syndrome Protein Family / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • CYFIP1 protein, human
  • GAS7 protein, human
  • Integrin beta1
  • Nerve Tissue Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Wiskott-Aldrich Syndrome Protein Family
  • Focal Adhesion Kinase 1
  • Proto-Oncogene Proteins pp60(c-src)