The NOGO receptor NgR2, a novel αVβ3 integrin effector, induces neuroendocrine differentiation in prostate cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 11 2022
07 11 2022
Historique:
received:
27
12
2021
accepted:
30
09
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
10
11
2022
Statut:
epublish
Résumé
Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, to which it associates; we also show that it promotes NED and anchorage-independent growth, as well as a motile phenotype of PrCa cells. Given our observations that high levels of αVβ3 and, as shown here, of NgR2 are detected in human and mouse NEPrCa, our findings appear to be highly relevant to this aggressive and metastatic subtype of PrCa. This study is novel because NgR2 role has only minimally been investigated in cancer and has instead predominantly been analyzed in neurons. These data thus pave new avenues toward a comprehensive mechanistic understanding of integrin-directed signaling during PrCa progression toward a NE phenotype.
Identifiants
pubmed: 36344556
doi: 10.1038/s41598-022-21711-5
pii: 10.1038/s41598-022-21711-5
pmc: PMC9640716
doi:
Substances chimiques
Androgen Antagonists
0
Integrins
0
RTN4RL2 protein, human
0
Nogo Receptor 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
18879Subventions
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL154811
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA224769
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK127589
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA220446
Pays : United States
Organisme : NIH HHS
ID : R01 CA234162
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211199
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA140043
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA163227
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA241486
Pays : United States
Informations de copyright
© 2022. The Author(s).
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