Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy.
Animals
Breast Neoplasms
/ genetics
CSK Tyrosine-Protein Kinase
/ genetics
Cell Line, Tumor
Cell Proliferation
Female
Humans
Lipogenesis
/ physiology
Male
Mammary Neoplasms, Animal
/ genetics
Mice, Mutant Strains
Mice, Transgenic
Phosphatidate Phosphatase
/ genetics
Phosphorylation
Proto-Oncogene Mas
Tyrosine
/ metabolism
Xenograft Model Antitumor Assays
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 11 2020
17 11 2020
Historique:
received:
17
02
2020
accepted:
21
09
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
17
12
2020
Statut:
epublish
Résumé
Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1
Identifiants
pubmed: 33203880
doi: 10.1038/s41467-020-19694-w
pii: 10.1038/s41467-020-19694-w
pmc: PMC7672079
doi:
Substances chimiques
MAS1 protein, human
0
Proto-Oncogene Mas
0
Tyrosine
42HK56048U
CSK Tyrosine-Protein Kinase
EC 2.7.10.2
CSK protein, human
EC 2.7.10.23
LPIN1 protein, human
EC 3.1.3.4
Lpin1 protein, mouse
EC 3.1.3.4
Phosphatidate Phosphatase
EC 3.1.3.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5842Références
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