Metastasis suppressor KAI1/CD82 attenuates the matrix adhesion of human prostate cancer cells by suppressing fibronectin expression and β1 integrin activation.

Abstract

KAI1/CD82, a tetraspanin membrane protein functions as a metastasis suppressor in many types of human cancers and has been shown to regulate cell adhesion properties. In the present study, we investigated the underlying mechanism of KAI1/CD82-mediated changes in cell adhesion to the extracellular matrix using human prostate cancer cells. We found that high KAI1/CD82 expression attenuated short-term cell adhesion to uncoated- or fibronectin-coated plates. Moreover, high KAI1/CD82 expression generated an extracellular environment unfavorable for cell adhesion as compared to low KAI1/CD82 expression, suggesting KAI1/CD82-dependent regulation of extracellular matrix (ECM) molecule(s) expression and/or secretion. Among ECM components examined, fibronectin exhibited decreased expression and secretion in high KAI1/CD82-expressing cells. Furthermore, high KAI1/CD82 expression interfered with the activation of β (1) integrin at the cell surface while total β (1) integrin levels remained unchanged, concomitant with reduced formation of focal adhesion complex and decreased bundling of actin filaments. Finally, high KAI1/CD82 expression significantly retarded cell motility in a scratch wound assay. Taken together, our results strongly suggest that KAI1/CD82 attenuates the activation of β (1) integrin, and thereby down-regulates outside-in signaling of β (1) integrin, leading to the reduction of focal adhesion formation and fibronectin expression/secretion, which subsequently interferes with cell adhesion properties and motility.

• Authors: Hyun-Ah Lee, Iha Park, Hee-Jung Byun, Dooil Jeoung, Young-Myeong Kim, Hansoo Lee
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 27 Issue 5 Pg. 575-86 ( 2011) ISSN: 1421-9778 [Electronic] Germany
• PMID: 21691075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Fibronectins
• Integrin beta1
• Kangai-1 Protein
• Lipids
• Lipofectamine

Topics

• Blotting, Western
• Cell Adhesion (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Extracellular Matrix (metabolism)
• Fibronectins (antagonists & inhibitors, genetics, metabolism)
• Focal Adhesions (metabolism)
• Gene Expression
• Gene Silencing
• Humans
• Integrin beta1 (genetics, metabolism)
• Kangai-1 Protein (genetics, metabolism)
• Lipids
• Male
• Microscopy, Confocal
• Plasmids
• Prostatic Neoplasms (genetics, metabolism, pathology, secondary)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (genetics)
• Transfection
• Up-Regulation