TY - JOUR
T1 - Src activity alters α3 integrin expression in colon tumor cells
AU - Kline, Christina Leah B.
AU - Olson, Thomas L.
AU - Irby, Rosalyn
N1 - Funding Information:
Acknowledgments I would like to acknowledge the Penn State University Functional Genomics and Flow Cytometry core facilities for Real Time PCR reactions and flow cytometry experiments. This work was partially funded by an internal grant given by the American Cancer Society: ACS-IRG Grant - #irg-93-032-07: The role of Src in Adhesion Molecules. I would also like to acknowledge Dr. Tim Ritty for the shRNA plasmid against α3 integrin and for many helpful conversations.
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
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U2 - 10.1007/s10585-008-9215-x
DO - 10.1007/s10585-008-9215-x
M3 - Article
C2 - 18839319
AN - SCOPUS:60449104053
SN - 0262-0898
VL - 26
SP - 77
EP - 87
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 2
ER -
