Abstract A53: Yin Yang 1 (YY1) regulates EMT via transcriptional activation of Snail and its overexpression in cancer stem cells (CSCs) in prostate cancer: Clinical significance.

Abstract

Abstract The epithelial to mesenchymal transition (EMT) is a cellular program that confers on neoplastic cells the biological traits needed to accomplish the metastatic cascade. The activation of EMT has been associated with the acquisition of stem cell traits, i.e., cancer stem cells (CSCs). CSCs have been reported to display EMT characteristics. Further, both EMT+ cells and CSCs exhibit a drug-resistant phenotype, hence, there is an urgent need to identify new therapeutic targets to eliminate both CSCs and EMT+ cells. Our previous findings and others’ demonstrated that the transcription factor Yin Yang 1 (YY1) regulates both the drug resistance and the metastasis-inducer Snail. Thus, we hypothesized that YY1 might be a multi-potential therapeutic target. We used human prostate carcinoma cell lines (PC3 EMT+ and LnCaP EMT-) as models. We demonstrate that overexpression of YY1 in LnCaP rendered the cells EMT+ (Snail+, E cadherin-, RKIP-). In contrast, treatment of PC3 with siRNA YY1 reverted the cells to the MET phenotype. Analysis by IHC in TMA of human prostate cancer tissues showed a positive correlation between the expression of Snail and YY1. Further, bioinformatic analysis corroborated the coexpression of Snail and YY1 in prostate cancer. Isolation of CSCs (CD44+, CD133+, CD24+) from PC3 cells exhibited overexpression of YY1 and other EMT markers. The inhibition of YY1 by various chemical inhibitors sensitized the resistant tumor cells to apoptosis to both chemo/immuno-cytotoxic drugs. These findings demonstrate that YY1 regulates EMT and drug resistance and is a prognostic biomarker. Further, we suggest that YY1 is a novel therapeutic target for the elimination of CSCs and metastasis in prostate cancer. Based on YY1 overexpression in many tumor types, we suggest that the present findings and their clinical significance may also be generalized to other cancers. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A53. Citation Format: Stavroula Baritaki, Valentina Rapozzi, Rosana Pelayo, Mario Vega, Sara Huerta-Yepez, Benjamin Bonavida. Yin Yang 1 (YY1) regulates EMT via transcriptional activation of Snail and its overexpression in cancer stem cells (CSCs) in prostate cancer: Clinical significance. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A53.