Downregulation of matriptase suppresses the PAR-2/PLCγ2/PKC-mediated invasion and migration abilities of MCF-7 breast cancer cells

Matriptases, members of the type II transmembrane serine protease family, are cell surface proteolytic enzymes that mediate tumor invasion and metastasis. Matriptase is highly expressed in breast cancer and is associated with poor patient outcome. However, the cellular mechanism by which matriptase mediates breast cancer invasion remains unknown. The present study aimed to determine the role of matriptase in the protein kinase C (PKC)-mediated metastasis of MCF-7 human breast cancer cells. Matriptase small interfering RNA-mediated knockdown significantly attenuated the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasiveness and migration of MCF-7 cells, and inhibited the activation of phospholipase C γ2 (PLCγ2)/PKC/MAPK signaling pathways. Matriptase-knockdown also suppressed the expression of MMP-9 and inhibited the activation of NF-κB/activator protein-1 in MCF-7 cells. Additionally, GB83 [an inhibitor of protease-activated receptor-2 (PAR-2)] inhibited PKC-mediated MMP-9 expression and metastatic ability in MCF-7 cells. Furthermore, downregulation of matriptase suppressed TPA-induced MMP-9 expression and invasiveness via PAR-2/PLCγ2/PKC/MAPK activation. These findings shed light on the mechanism underlying the role of matriptase in MCF-7 cell invasion and migration ability, and suggest that matriptase modulation could be a promising therapeutic strategy for preventing breast cancer metastasis.

• Publication year

  2021

• Venue

  Oncology Report

• Publication date

  2021-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3892/or.2021.8198PMID 34608498PMCID 8524316
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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