Abstract 1642: Calponin-3, acidic (CNN3) mediates EMT-related genes in human colorectal cancer metastasis

Abstract

Abstract (a) An introductory sentence indicating the purposes of the study Distant metastasis is the major cause of cancer-related death in colorectal cancer (CRC) patients. Although the Calponin family has emerged as a distinguishing feature in epithelial-to-mesenchymal transition (EMT) in human cancer, the role of CNN3 member in the metastatic CRC has not been investigated. (b) A brief description of pertinent experimental procedures. Three pairs of primary CRC and corresponding matched metastasis cell lines were analyzed for gene expression by microarray and western blotting. CNN3 was transduced to CRC cell line with lower CNN3 expression level (SW-480), and CNN3 with higher CNN3 expression CRC cell lines (SW-620, HCT-116) was suppressed by lentiviral-induced shRNA. Functional analysis of CNN3 overexpression and suppression was investigated in these CRC cell lines for proliferation and invasion. Expression of several potential CNN3 target genes (ERK1/2) and EMT markers (E-cadherin and vimentin) in primary CRC and matching metastasis CRC cell lines was validated. (c) A summary of the new, unpublished data. Global CNN3 expression levels were significantly higher in metastasis cell lines compared with the matched primary cell lines in both mRNA (FC = 2.3, p = 0.017) and protein levels. CRC cell lines with suppressed CNN3 showed decreased cell proliferation and reduced invasive behavior in CRC cell lines. Suppression of CNN3 in CRC cell lines with higher CNN3 expression resulted in increased E-cadherin and decreased vimentin. pERK1/2 were decreased in accordance with suppression of CNN3 in both SW-620 and HCT-116. Overexpression of CNN3 in CRC cell lines caused reduced E-cadherin in SW-480 and HT-29. (d) A statement of the conclusions CNN3 is involved in mediating EMT and metastatic behavior in the colon. Its expression is accordantly related to EMT markers, and CNN3 may serve as a possible diagnostic marker and therapeutic target for patients with CRC. Citation Format: Soon-Chan Kim, Chang-Won Hong, Sang-Geun Jang, Yeh-Ah Kim, Seung-Yong Jung, Jea-Gab Park, Ja-Lok Ku. Calponin-3, acidic (CNN3) mediates EMT-related genes in human colorectal cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1642.