Abstract 3798: Shift of Cx43 isoform expression by PQ1 in SW480 human colorectal cancer cells

Abstract

Abstract Colorectal cancer is one of the most common cancers in men and women in the United States. On average, the risk of developing colorectal cancer is about 1 in 20 over an individuals' lifetime. Cancer cells exhibit many deficiencies in cell-to-cell communication, particularly gap junctional intercellular communication (GJIC). GJIC has been reported to diminish as cancer cells progress. Gap junctions are intercellular channels composed of connexin proteins, which mediate the direct passage of small molecules from one cell to the next. They are involved in the regulation of cell cycle, cell differentiation, and cell signaling. Previously, a class of substituted quinolines, known as PQs, demonstrated to increase GJIC in cancer cells and subsequently attenuated tumor growth. The goal of this study is to determine whether the mode of PQ1 is by directly regulating the connexin protein. The results show that the low expression of connexin 43 (Cx43) in SW480 human colorectal cancer cells remains constant in the presence of PQ1. However, PQ1 caused a change in isoform expression of Cx43 in which there was a shift of Cx43 expression from P0 to P1 and P2 isoforms. This suggests that the trafficking of Cx43 from the Golgi to the membrane occurs in the presence of PQ1. Furthermore, the results show that Cx43 interacts with PKCα in SW480 cells; however, PQ1 does not affect the interaction of Cx43 and PKCα, suggesting that the shift in Cx43 isoforms is not due to PKCα phosphorylation. These findings provide in part that the increase of GJIC by PQ1 is due to the shift in Cx43 from P0 to P1 and P2 isoforms in SW480 colorectal cancer cells. Citation Format: Kristina M. Bigelow, Thu Annelise Nguyen. Shift of Cx43 isoform expression by PQ1 in SW480 human colorectal 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 3798. doi:10.1158/1538-7445.AM2014-3798