PMID- 25643809
OWN - NLM
STAT- MEDLINE
DCOM- 20160125
LR  - 20211203
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 35
IP  - 2
DP  - 2015 Mar 18
TI  - Signalling mechanisms regulating phenotypic changes in breast cancer cells.
LID - 10.1042/BSR20140172 [doi]
LID - e00178
AB  - 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 citrate 
      lyase (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.
FAU - Volinsky, Natalia
AU  - Volinsky N
AD  - *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Republic 
      of Ireland.
FAU - McCarthy, Cormac J
AU  - McCarthy CJ
AD  - *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Republic 
      of Ireland.
FAU - von Kriegsheim, Alex
AU  - von Kriegsheim A
AD  - *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Republic 
      of Ireland.
FAU - Saban, Nina
AU  - Saban N
AD  - *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Republic 
      of Ireland.
FAU - Okada-Hatakeyama, Mariko
AU  - Okada-Hatakeyama M
AD  - daggerLaboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical 
      Sciences (IMS), Tsurumi-ku, Yokohama, Kanagawa, Japan.
FAU - Kolch, Walter
AU  - Kolch W
AD  - *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Republic 
      of Ireland.
FAU - Kholodenko, Boris N
AU  - Kholodenko BN
AD  - *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Republic 
      of Ireland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150318
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Insulin)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (NRG1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Neuregulin-1)
RN  - EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - ATP Citrate (pro-S)-Lyase/genetics/metabolism
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Female
MH  - Humans
MH  - Insulin/genetics/metabolism
MH  - *MAP Kinase Signaling System
MH  - MCF-7 Cells
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Multiprotein Complexes/genetics/metabolism
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Neuregulin-1/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC4370098
EDAT- 2015/02/04 06:00
MHDA- 2016/01/26 06:00
CRDT- 2015/02/04 06:00
PHST- 2015/02/04 06:00 [entrez]
PHST- 2015/02/04 06:00 [pubmed]
PHST- 2016/01/26 06:00 [medline]
AID - BSR20140172 [pii]
AID - e00178 [pii]
AID - 10.1042/BSR20140172 [doi]
PST - epublish
SO  - Biosci Rep. 2015 Mar 18;35(2):e00178. doi: 10.1042/BSR20140172.