HePTP promotes migration and invasion in triple-negative breast cancer cells via activation of Wnt/β-catenin signaling

Biomed Pharmacother. 2019 Oct:118:109361. doi: 10.1016/j.biopha.2019.109361. Epub 2019 Aug 23.

Abstract

Aim: Cancer metastasis remains a major challenge for the clinical management of breast cancer, especially triple-negative breast cancer (TNBC), and the underlying molecular mechanisms remain largely unknown. The aim of this study was to explore the mechanism of TNBC metastasis.

Main methods: The expression of protein tyrosine phosphatase, non-receptor type 7 (HePTP) was detected using real time-PCR, western blot. Wound healing assay and transwell matrix assay were used to evaluate the pro-migration and pro-invasion potential of HePTP in vitro. Luciferase activity assay and nuclear extract analysis were used to evaluate Wnt/β-catenin signaling activity.

Key findings: We reported that HePTP was overexpressed in TNBC, where it acted to drive migration and invasion of tumor cells. We showed that knockdown of HePTP significantly suppressed metastatic capacity of TNBC cells. Moreover, HePTP promoted cells migration and invasion by dephosphorylating glycogen synthase kinase 3 beta (GSK3β), thereby activating Wnt/β-catenin signaling. Additionally, we demonstrated that overexpression of HePTP in HePTP lowly expressed cells could effectively promote the migration and invasion of breast cancer cells.

Significance: Our results suggest that HePTP plays a key role in the metastasis of TNBC via activating Wnt/β-catenin signaling. Hence, we propose that HePTP may serve as a novel prognostic marker and a potential therapeutic target for the treatment of TNBC.

Keywords: HePTP; Invasion; Migration; Triple-negative breast cancer; Wnt/β-catenin.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement*
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Neoplasm Invasiveness
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology*
  • Up-Regulation / genetics
  • Wnt Signaling Pathway*

Substances

  • PTPN7 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor