@article{5d5e398c9c8d4d08be209d80bf0b97bb,
title = "The Crosstalk of mTOR/S6K1 and Hedgehog Pathways",
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.",
author = "Yan Wang and Qingqing Ding and Yen, {Chia Jui} and Weiya Xia and Izzo, {Julie G.} and Lang, {Jing Yu} and Li, {Chia Wei} and Hsu, {Jennifer L.} and Miller, {Stephanie A.} and Xuemei Wang and Lee, {Dung Fang} and Hsu, {Jung Mao} and Longfei Huo and LaBaff, {Adam M.} and Dongping Liu and Huang, {Tzu Hsuan} and Lai, {Chien Chen} and Tsai, {Fuu Jen} and Chang, {Wei Chao} and Chen, {Chung Hsuan} and Wu, {Tsung Teh} and Buttar, {Navtej S.} and Wang, {Kenneth K.} and Yun Wu and Huamin Wang and Jaffer Ajani and Hung, {Mien Chie}",
note = "Funding Information: We thank Dr. Anthony E. Oro for providing the Gli1-expressing plasmid; Rune Toftg{\aa}rd for SuFu-expressing plasmid; and Dr. Hiroshi Sasaki for Gli1-reporter plasmids. We thank Jer-Yen Yang for insightful discussion and Su Zhang, Jian-Guang Shi, Zhen-Bo Han, and Jin-Fong Lee for technical assistance. This work was supported by the National Institutes of Health (CA109311and CA099031 to M.-C.H and CCSG Core Grant CA16672); the Kadoorie Charitable Foundation; the Center for Biological Pathway at the University of Texas, MD Anderson Cancer Center; Susan G. Komen (SAC110016 to M.-C.H), the Sister Institution Fund of China Medical University and Hospital and the University of Texas, MD Anderson Cancer Center; Department of Health Cancer Research Center of Excellence (DOH101-TD-C-111-005, Taiwan; NSC100-2321-B-039-002, Taiwan; NSC99-2632-B-039-001-MY3, Taiwan); the Dallas, Park, Sultan, Smith, and Cantu Family funds (to J.A.); the Reivercreek and Schecter Private foundations (to J.A.); Kevin and Frazier funds (to J.A.); National Cancer Institute (CA142072, CA127672, and CA129906 to J.A.); and the University of Texas, MD Anderson Cancer Center Multidisciplinary Research Program Funding. ",
year = "2012",
month = mar,
day = "20",
doi = "10.1016/j.ccr.2011.12.028",
language = "English (US)",
volume = "21",
pages = "374--387",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}