title: 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.affiliation: Medical & Bio-Material Research Center, College of Natural Sciences, School of Medicine, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea.
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Lee
authors.forename: Iha
authors.initials: I
authors.lastname: Park
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Byun
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051861:Kangai-1 Protein / Q000235:genetics / Q000378:metabolism; D008055:Lipids; D008297:Male; D018613:Microscopy, Confocal; D010957:Plasmids; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D051861:Kangai-1 Protein; D008055:Lipids; C086724:Lipofectamine