Thymosin beta 4 induces colon cancer cell migration and clinical metastasis via enhancing ILK/IQGAP1/Rac1 signal transduction pathway

Cancer Lett. 2011 Sep 28;308(2):162-71. doi: 10.1016/j.canlet.2011.05.001. Epub 2011 May 28.

Abstract

Thymosin β(4) (Tβ(4)) overexpression increases cell migration and tumor metastasis. Hence, understanding the mechanism of cancer cell migration induced by Tβ(4) may provide means to inhibit their metastasis. We demonstrated higher Rac1 activities and expression levels of IQGAP1 and ILK in highly migrated Tβ(4)-overexpressing SW480 cells. In addition, IQGAP1 formed a complex with ILK and knockdown of Tβ(4) simultaneously reduced ILK and IQGAP1 protein levels as well as their migration ability. These findings suggest that Tβ(4) increases migration of colon cancer cells via activating Rac1 by elevating IQGAP1/ILK complexes and IHC results illustrated a similar mechanism occurring in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Colonic Neoplasms / physiopathology*
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Protein Serine-Threonine Kinases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Thymosin / genetics
  • Thymosin / metabolism*
  • Tumor Cells, Cultured
  • Up-Regulation
  • rac1 GTP-Binding Protein / metabolism*
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • IQ motif containing GTPase activating protein 1
  • ras GTPase-Activating Proteins
  • thymosin beta(4)
  • Thymosin
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases
  • rac1 GTP-Binding Protein