2012
DOI: 10.1016/j.ccr.2011.12.028
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The Crosstalk of mTOR/S6K1 and Hedgehog Pathways

Abstract: Summary Esophageal adenocarcinoma (EAC) is the most prevalent esophageal cancer type in the United States. 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. Moreove… Show more

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Cited by 329 publications
(388 citation statements)
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“…Our results show that DGT inhibits activation of GSK3b by increasing the phosphorylation level. Gli1 has been reported to be activated by many kinases, such as AKT, MAPK/ERK, and mTOR/S6K1 (42,47). In this study, we were able to show a link between GSK3b and Gli1.…”
Section: Discussionsupporting
confidence: 66%
See 1 more Smart Citation
“…Our results show that DGT inhibits activation of GSK3b by increasing the phosphorylation level. Gli1 has been reported to be activated by many kinases, such as AKT, MAPK/ERK, and mTOR/S6K1 (42,47). In this study, we were able to show a link between GSK3b and Gli1.…”
Section: Discussionsupporting
confidence: 66%
“…The HH signal pathway is also considered to be crucially involved in the development and progression of many cancers because it is overactivated and correlated with growth and metastasis (36,42,43). Activated Gli proteins, primarily Gli1, translocate into the nucleus and stimulate the transcription of HH pathway target genes, including Gli1, PTCH1, and many survival-promoting molecules (44)(45)(46).…”
Section: Discussionmentioning
confidence: 99%
“…As well, the S6K1 pathway is related to Gli1-mediated proliferation of esophageal adenocarcinoma cells, supporting the role of S6K1 in cancer cell proliferation. 23,24 In addition, cell cycle progression was severely blocked in liverspecific S6 knockout mice after hepatectomy, 25 indicating the critical role of S6 in cell cycle progression. At present, it remains unclear how S6 and its phosphorylation control cell cycle regulators in esophageal cancer.…”
Section: Discussionmentioning
confidence: 99%
“…Activated Gli proteins eventually translocate into the nucleus and trigger the transcription of downstream target genes (5,7). In addition to classical HH signal transduction, the non-canonical HH pathway, in which Gli proteins are regulated by phosphoinositide 3-kinase (PI3K)/V-Akt murine thymoma viral oncogene (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), nuclear factor κB (NF-κB) and/or transforming growth factor β (TGFβ) pathways as well as the key tumor suppressors tumor protein p53 (TP53) and phosphatase and tensin homolog (PTEN) in a ligand-independent manner, has been the focus of previous research (8)(9)(10). Although the canonical pathway has been well-investigated, how Gli proteins are regulated in a SMO-independent manner in prostate cancer remains largely unknown.…”
Section: Introductionmentioning
confidence: 99%