DLC1 deficiency and YAP signaling drive endothelial cell contact inhibition of growth and tumorigenesis.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic
/ genetics
Contact Inhibition
Endothelial Cells
/ metabolism
Female
GTPase-Activating Proteins
/ genetics
Hemangiosarcoma
/ genetics
Human Umbilical Vein Endothelial Cells
Humans
Mice
Mice, Inbred BALB C
Signal Transduction
Transcription Factors
/ genetics
Tumor Suppressor Proteins
/ genetics
YAP-Signaling Proteins
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
19
11
2018
accepted:
27
05
2019
revised:
12
04
2019
pubmed:
15
8
2019
medline:
3
3
2020
entrez:
15
8
2019
Statut:
ppublish
Résumé
Deleted in Liver Cancer 1 (DLC1) is a tumor suppressor gene deleted in many cancers, including angiosarcoma, an aggressive malignancy of endothelial cell derivation. DLC1-deficiency in primary endothelial cells causes the loss of cell contact inhibition of growth through incompletely defined mechanisms. We report that DLC1 is a regulator of YAP, a transcriptional coactivator of proliferation-promoting and tumor-promoting genes; when confluent, active/nuclear YAP was significantly more abundant in DLC1-deficient endothelial cells compared with control cells. We also found that YAP is a required effector of the loss of cell contact inhibition of growth manifested by DLC1-deficient endothelial cells, as the silencing of YAP prevents this loss. Consistently, human angiosarcomas specimens contained a significantly greater proportion of DLC1
Identifiants
pubmed: 31409902
doi: 10.1038/s41388-019-0944-x
pii: 10.1038/s41388-019-0944-x
pmc: PMC8276116
mid: NIHMS1715426
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
DLC1 protein, human
0
GTPase-Activating Proteins
0
Transcription Factors
0
Tumor Suppressor Proteins
0
YAP-Signaling Proteins
0
YAP1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7046-7059Subventions
Organisme : Intramural NIH HHS
ID : ZIA SC010355
Pays : United States
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