Abstract 168: MALAT1 is crucial for epithelial-mesenchymal transition of breast cancer cells in acidic microenvironment

Abstract

Abstract Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is found up-regulated in several tumors. However, little is known about the role of MALAT1 in breast cancer, which is one of the highly invasive tumors among women worldwide. In this study, we found that MALAT1 was highly expressed in both breast cancer cell lines and breast cancer specimens in comparison to normal specimens. We found that low extracellular pH (pHe-acidosis), a major hallmark of solid tumors, further up-regulates MALAT-1 in several breast cancer cell lines in a time-dependent manner. Furthermore, acidosis induces epithelial to mesenchymal transition (EMT)-associated vimentin and Twist 1 expression but suppresses E-cadherin levels in breast cancer cells. Moreover, breast cancer cells under low pHe adopt stem-ness property as revealed by an increase in CD44+ and ESA+ population, mammosphere formation, and expression of OCT-4, SOX-2 and Nanog. Acidosis promotes translocation of β-catenin from cytoplasm to nucleus. The antisense oligonucleotides mediated gene silencing of MALAT-1 prevents acidosis induced nuclear translocation of β-catenin. This is in consistent with our previous finding that breast cancer cells cultured under low pHe exhibit an increased invasion activity. These results suggest that acidosis-induced MALAT-1 trigger an EMT program, leading to cell invasion and metastasis. Therefore, MALAT-1 represents a potential target for breast cancer therapy. Studies are underway to delineate the mechanistic association between MALAT-1, β-catenin, and EMT in acidic microenvironment. Citation Format: Subash C. Gupta, Yin-Yuan Mo. MALAT1 is crucial for epithelial-mesenchymal transition of breast cancer cells in acidic microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 168. doi:10.1158/1538-7445.AM2015-168