Cancer cell invasion in three-dimensional collagen is regulated differentially by Gα13 protein and discoidin domain receptor 1-Par3 protein signaling

Christina R. Chow, Kazumi Ebine, Lawrence M. Knab, David J. Bentrem, Krishan Kumar, Hidayatullah G. Munshi*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Cancer cells can invade in three-dimensional collagen as single cells or as a cohesive group of cells that require coordination of cell-cell junctions and the actin cytoskeleton. To examine the role of Gα13, a G12 family heterotrimeric G protein, in regulating cellular invasion in three-dimensional collagen, we established a novel method to track cell invasion by membrane type 1 matrix metalloproteinase-expressing cancer cells. We show that knockdown of Gα13 decreased membrane type 1 matrix metalloproteinase-driven proteolytic invasion in three-dimensional collagen and enhanced E-cadherin-mediated cell-cell adhesion. E-cadherin knockdown reversed Gα13 siRNA-induced cell-cell adhesion but failed to reverse the effect of Gα13 siRNA on proteolytic invasion. Instead, concurrent knockdown of E-cadherin and Gα13 led to an increased number of single cells rather than groups of cells. Significantly, knockdown of discoidin domain receptor 1 (DDR1), a collagen-binding protein that also co-localizes to cell-cell junctions, reversed the effects of Gα13 knockdown on cell-cell adhesion and proteolytic invasion in three-dimensional collagen. Knockdown of the polarity protein Par3, which can function downstream of DDR1, also reversed the effects of Gα13 knockdown on cell-cell adhesion and proteolytic invasion in three-dimensional collagen. Overall, we show that Gα13 and DDR1-Par3 differentially regulate cellcell junctions and the actin cytoskeleton to mediate invasion in three-dimensional collagen.

Original languageEnglish (US)
Pages (from-to)1605-1618
Number of pages14
JournalJournal of Biological Chemistry
Volume291
Issue number4
DOIs
StatePublished - Jan 22 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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