The Crosstalk of mTOR/S6K1 and Hedgehog Pathways

Yan Wang, 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 & 7 others Tsung Teh Wu, Navtej Singh Buttar, Kenneth Ke Ning Wang, Yun Wu, Huamin Wang, Jaffer Ajani, Mien Chie Hung

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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.

Original languageEnglish (US)
Pages (from-to)374-387
Number of pages14
JournalCancer Cell
Volume21
Issue number3
DOIs
StatePublished - Mar 20 2012

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Adenocarcinoma
Esophageal Neoplasms
Phosphorylation
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Wang, Y., Ding, Q., Yen, C. J., Xia, W., Izzo, J. G., Lang, J. Y., ... Hung, M. C. (2012). The Crosstalk of mTOR/S6K1 and Hedgehog Pathways. Cancer Cell, 21(3), 374-387. https://doi.org/10.1016/j.ccr.2011.12.028

The Crosstalk of mTOR/S6K1 and Hedgehog Pathways. / Wang, Yan; Ding, Qingqing; Yen, Chia Jui; Xia, Weiya; Izzo, Julie G.; Lang, Jing Yu; Li, Chia Wei; Hsu, Jennifer L.; Miller, Stephanie A.; Wang, Xuemei; Lee, Dung Fang; Hsu, Jung Mao; Huo, Longfei; LaBaff, Adam M.; Liu, Dongping; Huang, Tzu Hsuan; Lai, Chien Chen; Tsai, Fuu Jen; Chang, Wei Chao; Chen, Chung Hsuan; Wu, Tsung Teh; Buttar, Navtej Singh; Wang, Kenneth Ke Ning; Wu, Yun; Wang, Huamin; Ajani, Jaffer; Hung, Mien Chie.

In: Cancer Cell, Vol. 21, No. 3, 20.03.2012, p. 374-387.

Research output: Contribution to journalArticle

Wang, Y, Ding, Q, Yen, CJ, Xia, W, Izzo, JG, Lang, JY, Li, CW, Hsu, JL, Miller, SA, Wang, X, Lee, DF, Hsu, JM, Huo, L, LaBaff, AM, Liu, D, Huang, TH, Lai, CC, Tsai, FJ, Chang, WC, Chen, CH, Wu, TT, Buttar, NS, Wang, KKN, Wu, Y, Wang, H, Ajani, J & Hung, MC 2012, 'The Crosstalk of mTOR/S6K1 and Hedgehog Pathways', Cancer Cell, vol. 21, no. 3, pp. 374-387. https://doi.org/10.1016/j.ccr.2011.12.028
Wang Y, Ding Q, Yen CJ, Xia W, Izzo JG, Lang JY et al. The Crosstalk of mTOR/S6K1 and Hedgehog Pathways. Cancer Cell. 2012 Mar 20;21(3):374-387. https://doi.org/10.1016/j.ccr.2011.12.028
Wang, Yan ; Ding, Qingqing ; Yen, Chia Jui ; Xia, Weiya ; Izzo, Julie G. ; Lang, Jing Yu ; Li, Chia Wei ; Hsu, Jennifer L. ; Miller, Stephanie A. ; Wang, Xuemei ; Lee, Dung Fang ; Hsu, Jung Mao ; Huo, Longfei ; LaBaff, Adam M. ; Liu, Dongping ; Huang, Tzu Hsuan ; Lai, Chien Chen ; Tsai, Fuu Jen ; Chang, Wei Chao ; Chen, Chung Hsuan ; Wu, Tsung Teh ; Buttar, Navtej Singh ; Wang, Kenneth Ke Ning ; Wu, Yun ; Wang, Huamin ; Ajani, Jaffer ; Hung, Mien Chie. / The Crosstalk of mTOR/S6K1 and Hedgehog Pathways. In: Cancer Cell. 2012 ; Vol. 21, No. 3. pp. 374-387.
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AU - Hung, Mien Chie

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