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A suppressive role of mitogen inducible gene-2 in mesenchymal cancer cell invasion

Xiaohua Shi1, Chuanyue Wu

  • 1707B Scaife Hall, Department of Pathology, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.

Molecular Cancer Research : MCR
|May 29, 2008
PubMed

Insights

Mitogen inducible gene-2 (Mig-2) suppresses mesenchymal cancer cell invasion by inhibiting urokinase-type plasminogen activator (uPA) secretion. Lower Mig-2 levels correlate with increased cancer cell invasiveness and metastasis potential.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Cancer cell invasion of the extracellular matrix (ECM) is a critical step in metastasis.
  • Focal adhesion protein Mig-2 (kindlin-2) expression is altered in human cancers.
  • The specific role of Mig-2 in mesenchymal cancer cell invasion remains unclear.

Purpose of the Study:

  • To investigate the role of Mig-2 in mesenchymal cancer cell invasion.
  • To determine the mechanism by which Mig-2 influences cancer cell invasiveness.

Main Methods:

  • Investigated Mig-2 expression in SK-LMS-1 and HT-1080 cancer cell lines.
  • Utilized in vitro Matrigel invasion assays to assess cell invasiveness.
  • Examined the effect of Mig-2 overexpression and knockdown on urokinase-type plasminogen activator (uPA) secretion and localization.

Main Results:

  • Mig-2 expression was inversely correlated with invasiveness; high in SK-LMS-1, low in HT-1080 cells.
  • Overexpression of Mig-2 reduced ECM invasion, while Mig-2 knockdown increased invasiveness.
  • Mig-2 inhibited uPA secretion and pericellular proteolysis by promoting uPA intracellular accumulation.

Conclusions:

  • Mig-2 acts as a suppressor of mesenchymal cancer cell invasion.
  • Altered Mig-2 expression influences cancer cell dissemination and metastasis.
  • Mig-2's mechanism involves regulating uPA secretion and activity at cell-ECM adhesions.

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