| Literature DB >> 22439934 |
Yan Wang1, Qingqing Ding, Chia-Jui Yen, Weiya Xia, Julie G Izzo, Jing-Yu Lang, Chia-Wei Li, Jennifer L Hsu, Stephanie A Miller, Xuemei Wang, Dung-Fang Lee, Jung-Mao Hsu, Longfei Huo, Adam M Labaff, Dongping Liu, Tzu-Hsuan Huang, Chien-Chen Lai, Fuu-Jen Tsai, Wei-Chao Chang, Chung-Hsuan Chen, Tsung-Teh Wu, Navtej S Buttar, Kenneth K Wang, Yun Wu, Huamin Wang, Jaffer Ajani, Mien-Chie Hung.
Abstract
Esophageal adenocarcinoma (EAC) is the most prevalent esophageal cancer type in the United States. The TNF-α/mTOR pathway is known to mediate the development of EAC. Additionally, aberrant activation of Gli1, downstream effector of the Hedgehog (HH) pathway, has been observed in EAC. In this study, we found that an 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 an mTOR pathway inhibitor enhances the killing effects of the HH pathway inhibitor. Together, our results established a crosstalk between the mTOR/S6K1 and HH pathways, which provides a mechanism for SMO-independent Gli1 activation and also a rationale for combination therapy for EAC. Copyright ÂEntities:
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Year: 2012 PMID： 22439934 PMCID： PMC3350095 DOI： 10.1016/j.ccr.2011.12.028
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743