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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.