The metastasis suppressor CD82/KAI1 inhibits fibronectin adhesion-induced epithelial-to-mesenchymal transition in prostate cancer cells by repressing the associated integrin signaling
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Jaeseob Lee1,*, Hee-Jung Byun1,*, Moon-Sung Lee2, Young-June Jin1, Dooil Jeoung3, Young-Myeong Kim4, Hansoo Lee1,2
1Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon, Kangwon-do 200-701, Republic of Korea
2BIT Medical Convergence Graduate Program, Kangwon National University, Chunchon, Kangwon-do 200-701, Republic of Korea
3Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon, Kangwon-do 200-701, Republic of Korea
4Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701, Republic of Korea
*These authors have contributed equally to this work
Hansoo Lee, email: [email protected]
Keywords: CD82, EMT, fibronectin matrix, integrin signaling, cancer invasion
Received: July 22, 2016 Accepted: November 14, 2016 Published: December 01, 2016
The transmembrane protein CD82/KAI1 suppresses the metastatic potential of various cancer cell types. Moreover, decrease or loss of CD82 expression is closely associated with malignancy and poor prognosis in many human cancers including prostate cancer. Despite intense scrutiny, the mechanisms underlying the metastasis-suppressing role of CD82 are still not fully understood. Here, we found that a fibronectin matrix induced mesenchymal phenotypes in human prostate cancer cells with no or low CD82 expression levels. However, high CD82 expression rendered prostate cancer cells to have intensified epithelial characteristics upon fibronectin engagement, along with decreased cell motility and invasiveness. The CD82 function of inhibiting fibronectin-induced epithelial-to-mesenchymal transition (EMT) was dependent not only on CD82 interactions with fibronectin-binding α3β1/α5β1 integrins but also on the integrin-mediated intracellular signaling events. Notably, CD82 attenuated the FAK-Src and ILK pathways downstream of the fibronectin-receptor integrins. Immunofluorescence staining of human prostate cancer tissue specimens illustrated a negative association of CD82 with EMT-related gene expression as well as prostate malignancy. Altogether, these results suggest that CD82 suppresses EMT in prostate cancer cells adhered to the fibronectin matrix by repressing adhesion signaling through lateral interactions with the associated α3β1 and α5β1 integrins, leading to reduced cell migration and invasive capacities.
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