Abstract 1957: Slug regulates SOX9 stability in lung carcinoma and its involvement in the regulation of cancer stem cells and lung metastasis

Abstract

Abstract Most solid tumors including lung carcinoma are believed to contain cancer stem cells (CSCs) that are responsible for tumor initiation, progression, and metastasis. Understanding how CSCs are regulated at the molecular level may lead to novel strategies for cancer therapy. We have identified two proteins, Slug and SOX9, which determine the CSC state of human lung cancer epithelial cells. Inhibition of either Slug or SOX9 sufficiently blocks CSCs in human lung carcinoma cell lines, as determined by side population and tumor sphere assays, and attenuates lung metastasis in vivo in a xenograft mouse model. Coexpression of Slug and SOX9 is detected in the majority of lung tissues with advanced stage carcinoma. Here we found for the first time that Slug regulates SOX9 stability. Loss of Slug results in SOX9 degradation through ubiquitin-proteasomal pathway, and overexpression of Slug conversely prevents SOX9 degradation. Together, our results provide a direct evidence for the control of CSCs and tumor progression by Slug and SOX9, and unveil a novel role of Slug in SOX9 stabilization. These findings provide a mechanistic insight to the pathogenesis of metastasis in advanced lung carcinoma. Citation Format: Sudjit Luanpitpong, Liying Wang, Yon Rojanasakul. Slug regulates SOX9 stability in lung carcinoma and its involvement in the regulation of cancer stem cells and lung metastasis. [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 1957. doi:10.1158/1538-7445.AM2014-1957