Signalling mechanisms regulating phenotypic changes in breast cancer cells

Title: Signalling mechanisms regulating phenotypic changes in breast cancer cells
Authors: Volinsky, Natalia
McCarthy, Cormac J.
Kriegsheim, Alex von
Saban, Nina
Okada-Hatakeyama, Mariko
Kolch, Walter
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 cancerCell fate decisionsLipid accumulationMCF-7mTORPI3 kinaseReceptor 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

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