Signalling mechanisms regulating phenotypic changes in breast cancer cells
Files in This Item:
|Signalling mechanisms regulating phenotypic changes in breast cancer cells KholodenkoB &KolchW.pdf||1.77 MB||Adobe PDF||Download|
|Title:||Signalling mechanisms regulating phenotypic changes in breast cancer cells||Authors:||Volinsky, Natalia
McCarthy, Cormac J.
Kriegsheim, Alex von
Kholodenko, Boris N.
|Permanent link:||http://hdl.handle.net/10197/9158||Date:||1-Apr-2015||Abstract:||In MCF-7 breast cancer cells epidermal growth factor (EGF) induces cell proliferation, whereas heregulin (HRG)/neuregulin (NRG) induces irreversible phenotypic changes accompanied by lipid accumulation. Although these changes in breast cancer cells resemble processes that take place in the tissue, there is no understanding of signalling mechanisms regulating it. To identify molecular mechanisms mediating this cell-fate decision process, we applied different perturbations to pathways activated by these growth factors. The results demonstrate that phosphoinositide 3 (PI3) kinase (PI3K) and mammalian target of rapamycin (mTOR) complex (mTORC)1 activation is necessary for lipid accumulation that can also be induced by insulin, whereas stimulation of the extracellular-signal-regulated kinase (ERK) pathway is surprisingly dispensable. Interestingly, insulin exposure, as short as 4 h, was sufficient for triggering the lipid accumulation, whereas much longer treatment with HRG was required for achieving similar cellular response. Further, activation patterns of ATP citratelyase (ACLY), an enzyme playing a central role in linking glycolytic and lipogenic pathways, suggest that lipids accumulated within cells are produced de novo rather than absorbed from the environment. In the present study, we demonstrate that PI3K pathway regulates phenotypic changes in breast cancer cells, whereas signal intensity and duration is crucial for cell fate decisions and commitment. Our findings reveal that MCF-7 cell fate decisions are controlled by a network of positive and negative regulators of both signalling and metabolic pathways.||Funding Details:||Science Foundation Ireland||Type of material:||Journal Article||Publisher:||Portland Press||Copyright (published version):||2015 the Authors||Keywords:||Breast cancer; Cell fate decisions; Lipid accumulation; MCF-7; mTOR; PI3 kinase; Receptor tyrosine kinases signalling pathways||DOI:||10.1042/BSR20140172||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
SBI Research Collection
Show full item record
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.