Oncogene Amplification in Growth Factor Signaling Pathways Renders Cancers Dependent on Membrane Lipid Remodeling.
1-Acylglycerophosphocholine O-Acyltransferase
/ genetics
A549 Cells
Animals
Cell Survival
/ genetics
ErbB Receptors
/ genetics
Female
Gene Amplification
Gene Expression Regulation, Neoplastic
Genotype
Heterografts
Humans
Mice
Mice, Nude
Neoplasms
/ genetics
Oncogenes
/ genetics
PC-3 Cells
Phospholipids
/ metabolism
Signal Transduction
/ genetics
Transfection
cancer dependency
cancer metabolism
gene amplification
growth factor signaling
membrane lipid remodeling
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
03 09 2019
03 09 2019
Historique:
received:
04
12
2018
revised:
28
04
2019
accepted:
12
06
2019
pubmed:
16
7
2019
medline:
22
8
2020
entrez:
16
7
2019
Statut:
ppublish
Résumé
Advances in DNA sequencing technologies have reshaped our understanding of the molecular basis of cancer, providing a precise genomic view of tumors. Complementary biochemical and biophysical perspectives of cancer point toward profound shifts in nutrient uptake and utilization that propel tumor growth and major changes in the structure of the plasma membrane of tumor cells. The molecular mechanisms that bridge these fundamental aspects of tumor biology remain poorly understood. Here, we show that the lysophosphatidylcholine acyltransferase LPCAT1 functionally links specific genetic alterations in cancer with aberrant metabolism and plasma membrane remodeling to drive tumor growth. Growth factor receptor-driven cancers are found to depend on LPCAT1 to shape plasma membrane composition through enhanced saturated phosphatidylcholine content that is, in turn, required for the transduction of oncogenic signals. These results point to a genotype-informed strategy that prioritizes lipid remodeling pathways as therapeutic targets for diverse cancers.
Identifiants
pubmed: 31303424
pii: S1550-4131(19)30317-1
doi: 10.1016/j.cmet.2019.06.014
pmc: PMC6742496
mid: NIHMS1532638
pii:
doi:
Substances chimiques
Phospholipids
0
epidermal growth factor receptor VIII
0
1-Acylglycerophosphocholine O-Acyltransferase
EC 2.3.1.23
Lpcat1 protein, human
EC 2.3.1.23
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
525-538.e8Subventions
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA211015
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS073831
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA231991
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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