ZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer.
Animals
Cadherins
/ metabolism
Carcinoma, Non-Small-Cell Lung
/ metabolism
Cell Line, Tumor
Co-Repressor Proteins
/ metabolism
Endocytosis
GTPase-Activating Proteins
/ metabolism
Humans
Lung Neoplasms
/ metabolism
Mi-2 Nucleosome Remodeling and Deacetylase Complex
/ metabolism
Mice
Models, Biological
Neoplasm Metastasis
Protein Binding
Zinc Finger E-box-Binding Homeobox 1
/ metabolism
rab GTP-Binding Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 11 2019
12 11 2019
Historique:
received:
01
03
2019
accepted:
29
09
2019
entrez:
14
11
2019
pubmed:
14
11
2019
medline:
28
2
2020
Statut:
epublish
Résumé
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, due in part to the propensity of lung cancer to metastasize. Aberrant epithelial-to-mesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell-cell adhesion is reduced allowing cells to dissociate and invade. Of the EMT-associated transcription factors, ZEB1 uniquely promotes NSCLC disease progression. Here we apply two independent screens, BioID and an Epigenome shRNA dropout screen, to define ZEB1 interactors that are critical to metastatic NSCLC. We identify the NuRD complex as a ZEB1 co-repressor and the Rab22 GTPase-activating protein TBC1D2b as a ZEB1/NuRD complex target. We find that TBC1D2b suppresses E-cadherin internalization, thus hindering cancer cell invasion and metastasis.
Identifiants
pubmed: 31719531
doi: 10.1038/s41467-019-12832-z
pii: 10.1038/s41467-019-12832-z
pmc: PMC6851102
doi:
Substances chimiques
Cadherins
0
Co-Repressor Proteins
0
GTPase-Activating Proteins
0
TBC1D2 protein, human
0
Zinc Finger E-box-Binding Homeobox 1
0
Mi-2 Nucleosome Remodeling and Deacetylase Complex
EC 3.5.1.98
rab GTP-Binding Proteins
EC 3.6.5.2
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
5125Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA214609
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37 CA214609-01A1
Pays : International
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