Inhibition of FASN and ERα signalling during hyperglycaemia-induced matrix-specific EMT promotes breast cancer cell invasion via a caveolin-1-dependent mechanism.
作者： H.A. Zielinska , J.M.P. Holly , A. Bahl , C.M. Perks
DOI: 10.1016/J.CANLET.2018.01.028
关键词: Cell growth 、 Cancer research 、 Signal transduction 、 Caveolin 1 、 Vimentin 、 Epithelial–mesenchymal transition 、 Cancer cell 、 Mesenchymal stem cell 、 Warburg effect 、 Chemistry
摘要: Since disturbed metabolic conditions such as obesity and diabetes can be critical determinants of breast cancer progression therapeutic failure, we aimed to determine the mechanism responsible for their pro-oncogenic effects. Using non-invasive, epithelial-like ERα-positive MCF-7 T47D human cells found that hyperglycaemia induced epithelial mesenchymal transition (EMT), a key programme development metastatic disease. This was demonstrated by loss marker E-cadherin together with increases in markers vimentin, fibronectin transcription factor SLUG, an enhancement cell growth invasion. These phenotypic changes were only observed grown on not those plated collagen. Analyzing parameters, hyperglycaemia-induced, matrix-specific EMT promoted Warburg effect upregulating glucose uptake, lactate release specific glycolytic enzymes transporters. We showed silencing fatty acid synthase (FASN) downstream ERα, which previously mediate hyperglycaemia-induced chemoresistance these cells, resulted suppression growth: however, this also dramatic invasion SLUG mRNA levels via novel caveolin-1-dependent mechanism.
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