Abstract 1287: High mobility of triple-negative breast cancer cells is due to repression of plakoglobin gene by SLUG

Abstract

Abstract One of highly pathogenic breast cancer cell types are the SLUG-high claudin-low triple negative (negative in the expression of estrogen, progesterone and ERBB2 receptors) breast cancer (TNBC) cells. These cells are highly metastatic and have low levels of the motility regulatory catenin plakoglobin. In order to link high levels of the transcriptional repressor SLUG in the TNBC cells with low levels of plakoglobin we found that SLUG inhibits the expression of plakoglobin gene directly in these cells and thus, among other downstream effects, help disseminating these tumor cells. Overexpression of SLUG in the SLUG-deficient cancer cells significantly decreased the levels of mRNA and protein of plakoglobin. On the contrary, knockdown of SLUG in SLUG-high cancer cells elevated the levels of plakoglobin. Overexpression of SLUG in the SLUG-deficient cells elevated the invasiveness and motility of these cells. On the other hand, knockdown of plakoglobin in these low motility non-invasive breast cancer cells did not affect the ability of the cancer cells to penetrate Matrigel matrix but increase the growth and migration rates of these cells. This study thus implicates high levels of SLUG and low levels of plakoglobin as determinants in the progression of highly disseminating breast cancer. Supported in parts by the DOD-CDMRP grants BC050641, BC086542 and BC103645 to GC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1287. doi:1538-7445.AM2012-1287