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Title

Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells

AuthorsCano-González, Ana ; López-Rivas, Abelardo
KeywordsApoptosis
TGF-β
Internalization
EGF
TRAIL
TRAIL-R2
Issue Date2016
PublisherElsevier
CitationBBA - Biochimica et Biophysica Acta 1863(8): 2104-2114 (2016)
AbstractTransforming growth factor-beta (TGF-β) induces the epithelial to mesenchymal transition (EMT) in breast epithelial cells and plays an important role in mammary morphogenesis and breast cancer. In non-transformed breast epithelial cells TGF-β antagonizes epidermal growth factor (EGF) action and induces growth inhibition. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to participate in lumen formation during morphogenesis of human breast epithelial cells. Our previous work indicated that sensitivity of human breast epithelial cells to TRAIL can be modulated through the activation of the epidermal growth factor receptor-1 (EGFR). Here, we show that TGF-β opposes EGF-mediated sensitization to TRAIL-induced caspase-8 activation and apoptosis in non-transformed breast epithelial cells. Death-inducing signalling complex (DISC) formation by TRAIL was significantly reduced in cells treated with TGF-β. TGF-β treatment activates cytoprotective autophagy and down-regulates TRAIL-R2 expression at the cell surface by promoting the intracellular accumulation of this receptor. Lastly, we demonstrate that EMT is not involved in the inhibitory effect of TGF-β on apoptosis by TRAIL. Together, the data reveal a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis.
URIhttp://hdl.handle.net/10261/165260
Identifiersdoi: 10.1016/j.bbamcr.2016.05.011
issn: 0006-3002
Appears in Collections:(CABIMER) Artículos
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