Abstract 1051: Metastasis suppressor CD82 functions as a negative regulator in the adhesion-dependent epithelial-to-mesenchymal transition in prostate cancer cells

Abstract

Abstract Tetraspanin CD82 suppresses cancer metastasis by inhibiting cell motility and invasiveness. In an effect to reveal the mechanism underlying the metastasis-suppressing role of CD82, we here examined the effect of CD82 on epithelial-mesenchymal transition (EMT), a critical event of cancer cells that promotes migration and invasion. In human prostate cancer cell lines, an increase in CD82 expression levels by exogenous gene delivery elevated E-cadherin levels, but decreased the levels of mesenchymal cell proteins including Snail, Twist, vimentin, N-cadhherin, and α-smooth muscle actin, suggesting EMT-suppressing role of CD82. Also, increased CD82 expression resulted in decreased motility and invasiveness of prostate cancer cells. In contrast, CD82 knockdown decreased E-cadherin levels, but increased the levels of mesenchymal cell proteins, together with cell morphology change to fibroblast-like shape. CD82 also interfered with TGF-β1- and Wnt-induced EMT. Additionally, CD82 decreased expression of β-catenin target genes such as c-myc and cyclin D1 by inhibiting nuclear translocation of β-catenin. Notably, the negative effect of CD82 on EMT was apparent on cells adhered to fibronectin. Fibronectin-binding α3β1/α5β1 integrins were involved in CD82-mediated inhibition of EMT. Importantly, human prostate cancer tissue specimens displayed a positive correlation of CD82 with E-cadherin expression levels, along with a negative correlation of CD82 with vimentin levels. Moreover, both CD82 and E-cadherin levels were inversely correlated with the malignant progression stages of human prostate cancers. Taken together, these results strongly suggest that CD82 suppresses motility and invasiveness of prostate cancer cells by inhibiting EMT in an α3β1/α5β1 integrin-dependent manner. Citation Format: Hee-Jung Byun, Yong-Sun Lee, Young-June Jin, Jae-Sub Lee, Young-Myeong Kim, Hansoo Lee. Metastasis suppressor CD82 functions as a negative regulator in the adhesion-dependent epithelial-to-mesenchymal transition in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1051. doi:10.1158/1538-7445.AM2014-1051