Profiling of subcellular EGFR interactome reveals hnRNP A3 modulates nuclear EGFR localization.
Journal
Oncogenesis
ISSN: 2157-9024
Titre abrégé: Oncogenesis
Pays: United States
ID NLM: 101580004
Informations de publication
Date de publication:
22 Apr 2020
22 Apr 2020
Historique:
received:
25
10
2019
accepted:
07
04
2020
revised:
04
04
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
24
4
2020
Statut:
epublish
Résumé
The aberrant subcellular translocation and distribution of epidermal growth factor receptor (EGFR) represent a major yet currently underappreciated cancer development mechanism in non-small cell lung cancer (NSCLC). In this study, we investigated the subcellular interactome of EGFR by using a spectral counting-based approach combined with liquid chromatography-tandem mass spectrometry to understand the associated protein networks involved in the tumorigenesis of NSCLC. A total of 54, 77, and 63 EGFR-interacting proteins were identified specifically in the cytosolic, mitochondrial, and nuclear fractions from a NSCLC cell line, respectively. Pathway analyses of these proteins using the KEGG database shown that the EGFR-interacting proteins of the cytosol and nucleus are involved in the ribosome and spliceosome pathways, respectively, while those of the mitochondria are involved in metabolizing propanoate, fatty acid, valine, leucine, and isoleucine. A selected nuclear EGFR-interacting protein, hnRNP A3, was found to modulate the accumulation of nuclear EGFR. Downregulation of hnRNP A3 reduced the nuclear accumulation of EGFR, and this was accompanied by reduced tumor growth ability in vitro and in vivo. These results indicate that variations in the subcellular translocation and distribution of EGFR within NSCLC cells could affect tumor progression.
Identifiants
pubmed: 32321917
doi: 10.1038/s41389-020-0225-0
pii: 10.1038/s41389-020-0225-0
pmc: PMC7176650
doi:
Types de publication
Journal Article
Langues
eng
Pagination
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