Abstract 5295: MELK enhances gastric cancer progression via the FAK/paxillin pathway

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Elevated MELK expression is a characteristic of multiple tumors and has been correlated with tumorigenesis and tumor development. However, the precise mechanism underlying this correlation is unclear. Here, we report that there are pleiotropic effects associated with enhanced MELK expression in gastric cancer, and this are mediated via the FAK/paxillin pathway. We first show that MELK mRNA and protein expression are both elevated in human gastric cancer, and this is associated with chemoresistance to 5-FU. Knockdown of MELK significantly suppresses cell proliferation, migration, and invasion of gastric cancer both in vitro and in vivo, and decreases the percentages of cells in the G1/G0 phase and increases those in the G2/M and S phases. Moreover, depletion of MELK decreases the amount of actin stress fibers and reduces RhoA activity. Finally, knockdown of MELK decreases the phosphorylation of molecular components of the FAK/Paxillin pathway and prevents gastrin-mediated FAK/paxillin phosphorylation. By contrast, MELK overexpression produces the opposite results, although the differences are moderate. Together, our work suggests that MELK plays an important role in the occurrence and development of gastric cancer, implicates the FAK/Paxillin pathway as the means by which it promotes these effects, and identifies MELK as a potential target for treatment against gastric cancer. Note: This abstract was not presented at the meeting. Citation Format: Bingya Liu, Tao Du, Ying Qu, Jian-fang Li, Liping Su, Zheng-gang Zhu. MELK enhances gastric cancer progression via the FAK/paxillin pathway. [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 5295. doi:10.1158/1538-7445.AM2014-5295