The Crosstalk of mTOR/S6K1 and Hedgehog Pathways
作者： Yan Wang , Qingqing Ding , Chia-Jui Yen , Weiya Xia , Julie G. Izzo
DOI: 10.1016/J.CCR.2011.12.028
关键词:
摘要: Esophageal adenocarcinoma (EAC) is the most prevalent esophageal cancer type in United States. The TNF-α/mTOR pathway known to mediate development of EAC. Additionally, aberrant activation Gli1, downstream effector Hedgehog (HH) pathway, has been observed In this study, we found that an activated mTOR/S6K1 promotes Gli1 transcriptional activity and oncogenic function through S6K1-mediated phosphorylation at Ser84, which releases from its endogenous inhibitor, SuFu. Moreover, elimination S6K1 by mTOR inhibitor enhances killing effects HH inhibitor. Together, our results established a crosstalk between pathways, provides mechanism for SMO-independent also rationale combination therapy
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