Abstract | BACKGROUND:
Phosphatidylinositol 3-kinase (PI3K), acting through the downstream kinase AKT, regulates a number of cellular processes such as cell growth and survival. Poorly differentiated colon cancers are characterized by increased integrin-mediated extracellular matrix interactions; disruption of this integrin-mediated adhesion leads to apoptosis and involves reduced PI3K activity. The purpose of this study was to determine: (1) the role of alpha5beta1 integrin expression on PI3K activity, and (2) whether blockade of alpha5beta1 integrin decreases colon cancer cell adhesion and increases apoptosis. METHODS: Human colon cancer cells were treated with anti-alpha5 integrin antibody, anti-beta1 integrin antibody, the PI3K inhibitor LY294002 (20 micromol/L), or wortmannin (400 nmol/L). Expression and function of alpha5 were quantitated by FACS analysis and cell adhesion assay, respectively. DNA fragmentation was measured to assess apoptosis. Protein was extracted to determine phosphorylated AKT (pAKT) expression as a measure of PI3K activity. RESULTS: CONCLUSION: Our results are the first to show that blockade of cell surface alpha5 integrin expression decreases PI3K activity, inhibits colon cancer cell attachment, and induces apoptosis. These findings suggest that agents which selectively target alpha5 integrin subunit expression may enhance the effects of standard chemotherapeutic agents and provide novel adjuvant treatment for selected colon cancers.
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Authors | Carlos A Murillo, Piotr G Rychahou, B Mark Evers |
Journal | Surgery
(Surgery)
Vol. 136
Issue 2
Pg. 143-9
(Aug 2004)
ISSN: 0039-6060 [Print] United States |
PMID | 15300173
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright 2004 Elsevier Inc. |
Chemical References |
- Integrin alpha5
- Phosphoinositide-3 Kinase Inhibitors
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Topics |
- Apoptosis
- Cell Adhesion
- Cell Line, Tumor
- Colonic Neoplasms
(pathology)
- Enzyme Activation
- Humans
- Integrin alpha5
(physiology)
- Phosphoinositide-3 Kinase Inhibitors
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