Serine protease modulation of Dependence Receptors and EMT protein expression

Kara McNair1, Caroline M Forrest1, Maria C J Vincenten1

  • 1a College of Medical, Veterinary and Life Sciences , University of Glasgow , Glasgow , UK.

Cancer Biology & Therapy
|November 8, 2018
PubMed

Insights

Serine proteases like chymotrypsin and subtilisin reduce Deleted in Colorectal Cancer (DCC) and neogenin expression, increasing cell migration. This migration isn't consistently linked to Epithelial-Mesenchymal Transition (EMT) markers, suggesting alternative pathways for cell movement.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumour suppressor Deleted in Colorectal Cancer (DCC) and neogenin are implicated in cell adhesion and migration.
  • Serine proteases can influence cellular processes, but their impact on DCC, neogenin, and Epithelial-Mesenchymal Transition (EMT) markers is not fully understood.

Purpose of the Study:

  • To investigate the association between serine protease activity (chymotrypsin, subtilisin) and the expression of DCC, neogenin, and EMT markers (E-cadherin, β-catenin, vimentin).
  • To determine if protease-induced cell migration is mediated by EMT.

Main Methods:

  • Treatment of tissue sections and cultured cells (MCF-7, MDA-MB-231, normal human breast cells) with chymotrypsin and subtilisin.
  • Analysis of DCC, neogenin, E-cadherin, β-catenin, and vimentin expression.
  • Assessment of cell migration using wound closure assays.
  • Transfection with a DCC-containing plasmid.

Main Results:

  • Chymotrypsin and subtilisin reduced DCC and neogenin expression and increased cell migration.
  • These proteases decreased β-catenin expression in tissue sections but not consistently in cultured cells; low serum also reduced β-catenin.
  • Vimentin expression increased with serine proteases and low serum in cancer cells, correlating with enhanced wound closure.
  • DCC transfection conferred resistance to β-catenin loss.

Conclusions:

  • Serine protease-induced cell migration is not consistently associated with changes in EMT markers, suggesting migration may occur independently of EMT.
  • The effect of serine proteases on EMT markers is context-dependent, varying between cell types and tissues.
  • EMT is not always directly correlated with cell migration.

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