Presentation Abstract

Abstract Number: 989
Presentation Title: The crosstalk of mTOR/S6K1 and Hedgehog pathways
Presentation Time: Sunday, Apr 01, 2012, 4:50 PM - 5:05 PM
Location: McCormick Place West (Level 1), Room W187
Author Block: Yan Wang, Weiya Xia, Jing-Yu Lang, Jennifer Hsu, Huamin Wang, Jaffer Ajani, Mien-Chie Hung. MD Anderson Cancer Center, Houston, TX
Abstract Body: Esophageal adenocarcinoma (EAC) is the most prevalent esophageal cancer type in the United States, and TNFα/mTOR pathway is known to mediate the development of EAC. Additionally, aberrant activation of Gli1, downstream effector of hedgehog pathway, has been observed in EAC. In this study, we found that activated mTOR/S6K1 pathway promotes Gli1 transcriptional activity and oncogenic function through S6K1-mediated Gli1 phosphorylation at Ser84, which releases Gli1 from its endogenous inhibitor, SuFu. Moreover, elimination of S6K1 activation by mTOR pathway inhibitor enhances the killing effects of the hedgehog pathway inhibitor. Together, our results established a crosstalk between mTOR/S6K1 and the hedgehog pathways, which provides not only a new mechanism for non-canonical hedgehog pathway but also a rationale for combination therapy for EAC.