Clinical & Experimental Metastasis

, Volume 26, Issue 2, pp 77–87 | Cite as

Src activity alters α3 integrin expression in colon tumor cells

  • Christina Leah B. Kline
  • Thomas L. Olson
  • Rosalyn B. Irby
Research Paper

Abstract

Src kinase has been linked to increased motility in the progression and metastasis of human colon cancer, although the mechanisms are not fully understood. Integrins are involved in metastasis by mediating attachment and migration of cells, as well as through transducing signals. This study examines the link between Src and integrin activity in the metastatic process in colon cancer cells. To determine Src involvement in integrin expression, the human colon cancer cell line, HCT116, was transfected with an activated Src construct and assayed for its ability to attach to and migrate across collagen and laminin. These cells attached more readily and migrated less rapidly on the extracellular matrix (ECM) than did cells transfected with empty vector. Examination of integrin levels showed a decrease in the α3 subunit in Src transfected cells as well as decreased cell surface localization of α3 integrin. The downregulation of α3 integrin was reversed by inhibition of Src and by inhibition of MAP kinase. Inhibition of α3 integrin using shRNA resulted in decreased MMP7 secretion, a possible cause of decreased invasion with low α3 integrin expression. This study shows that Src overexpression downregulates α3 integrin total protein expression and localization to the cell surface of HCT116 colon cancer cells. This indicates that Src activity may enhance metastasis by altering α3 integrin expression.

Keywords

Adhesion Colon cancer Integrin regulation Metastasis Migration MMP7 Src kinase 

Abbreviations

ECM

Extracellular matrix

ATCC

American type culture collection

PBS

Phosphate buffered saline

ATP

Adenosine triphosphate

RT PCR

Reverse transcriptase polymerase chain reaction

MAPK

Mitogen activated protein kinase

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Christina Leah B. Kline
    • 1
  • Thomas L. Olson
    • 1
  • Rosalyn B. Irby
    • 1
  1. 1.Department of Medicine, Penn State Hershey Cancer Institute, H072The Pennsylvania State University College of MedicineHersheyUSA

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