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10.12659/msm.901542

http://scihub22266oqcxt.onion/10.12659/msm.901542
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suck abstract from ncbi


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pmid28446743
      Med+Sci+Monit 2017 ; 23 (ä): 2017-2028
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  • Mammalian Target of Rapamycin (mTOR) Regulates Transforming Growth Factor-?1 (TGF-?1)-Induced Epithelial-Mesenchymal Transition via Decreased Pyruvate Kinase M2 (PKM2) Expression in Cervical Cancer Cells #MMPMID28446743
  • Cheng KY ; Hao M
  • Med Sci Monit 2017[Apr]; 23 (ä): 2017-2028 PMID28446743 show ga
  • BACKGROUND Epithelial-mesenchymal transition (EMT) plays an important role in cancer tumorigenesis. Transforming growth factor ?1 (TGF-?1) can induced EMT, which could increase tumor migration and invasion. Moreover, recent studies have been proven that mammalian target of rapamycin (mTOR) is a critical regulator of EMT. We investigated the mechanisms of mTOR in transforming growth factor ?1 (TGF-?1)-induced EMT in cervical cancer cells. MATERIAL AND METHODS HeLa and SiHa cells were treated with 10 ng/ml TGF-?1 to induce EMT. Then, they were treated with or without rapamycin. CCK8 assay was performed to determine cell proliferation. Cell migration was detected by wound-healing assay; apoptosis was analyzed by flow cytometry; mTOR inhibitors inhibited mTOR pathway to assess the expression of E-cadherin, Vimentin STAT3, Snail2, p-p70s6k, and PKM2 expression. RESULTS TGF-?1 promoted proliferation and migration, and attenuated apoptosis in cervical carcinoma cells. Rapamycin abolished TGF-?1-induced EMT cell proliferation and migration and reversed TGF-?1-induced EMT. E-cadherin were suppressed, whereas Vimentin and PKM2 were increased in HeLa and SiHa cells after stimulation with TGF-?1. Moreover, mTOR was activated in the process of TGF-?1-induced EMT. Rapamycin inhibited the phosphorylation of p70s6k. Furthermore, inhibition of the mTOR pathway decreased PKM2 expression. CONCLUSIONS Inhibition of the mTOR pathway abolished TGF-?1-induced EMT and reduced mTOR/p70s6k signaling, which downregulated PKM2 expression. Our results provide novel mechanistic insight into the anti-tumor effects of inhibition of mTOR.
  • |Apoptosis/drug effects [MESH]
  • |Cadherins/metabolism [MESH]
  • |Carrier Proteins/biosynthesis/genetics/*metabolism [MESH]
  • |Cell Line, Tumor [MESH]
  • |Cell Movement/drug effects [MESH]
  • |Cell Proliferation/drug effects [MESH]
  • |Epithelial-Mesenchymal Transition/*drug effects [MESH]
  • |Female [MESH]
  • |HeLa Cells [MESH]
  • |Humans [MESH]
  • |Membrane Proteins/biosynthesis/genetics/*metabolism [MESH]
  • |Ribosomal Protein S6 Kinases, 70-kDa/metabolism [MESH]
  • |Signal Transduction/drug effects [MESH]
  • |Sirolimus/pharmacology [MESH]
  • |TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism [MESH]
  • |Thyroid Hormone-Binding Proteins [MESH]
  • |Thyroid Hormones/biosynthesis/genetics/*metabolism [MESH]
  • |Transforming Growth Factor beta1/*pharmacology [MESH]


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