Overexpressed transient receptor potential vanilloid 1 (TRPV1) in lung adenocarcinoma harbours a new opportunity for therapeutic targeting.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
21
09
2021
accepted:
09
03
2022
revised:
26
02
2022
pubmed:
1
4
2022
medline:
20
10
2022
entrez:
31
3
2022
Statut:
ppublish
Résumé
The specific biological function of transient receptor potential vanilloid 1 (TRPV1) in pathogenesis of lung adenocarcinoma (LUAD) remains unclear. In this study, TRPV1 expression in tumor tissues, primary cells and cell lines of LUAD, as well as the mechanism mediating its hyperexpression were systematically studied. Multiple models and techniques were adopted to elucidate the relationship between TRPV1 hyperexpression and tumor recurrence and metastasis. Results showed that TRPV1 expression was increased in tumor tissues and primary tumor cells of LUAD patients. The increased expression was associated with worse overall survival outcome and raised HIF1α levels. TRPV1 expression in A549 and NCI-H292 cells was increased after pretreatment with cigarette smoke extract or spermine NONOate. Moreover, A549 cells with TRPV1 overexpression has enhanced tumor growth rates in subcutaneous grafted tumor models, and increased intrapulmonary metastasis after tail vein infusion in nude BALB/c nude mice. Mechanistically, TRPV1 overexpression in A549 cells promoted HIF1α expression and nuclear translocation by promoting CREB phosphorylation and activation of NOS1-NO pathway, ultimately leading to accelerated cell proliferation and stronger invasiveness. In addition, based on photothermal effects, CuS-TRPV1 mAb effectively targeted and induced apoptosis of TRPV1-A549 cells both in vivo and in vitro, thereby mitigating tumor growth and metastasis induced by xenotransplantation of TRPV1-A549 cells. In conclusion, TRPV1 hyperexpression in LUAD is a risk factor for tumor progression and is involved in proliferation and migration of tumor cells through activation of HIF1α. Our study also attempted a new strategy inhibiting the recurrence and metastasis of LUAD: by CuS-TRPV1 mAb precisely kill TRPV1 hyperexpression cells through photothermal effects.
Identifiants
pubmed: 35354949
doi: 10.1038/s41417-022-00459-0
pii: 10.1038/s41417-022-00459-0
pmc: PMC9576597
doi:
Substances chimiques
Copper
789U1901C5
cupric sulfide
KL4YU612X7
TRPV Cation Channels
0
TRPV1 protein, mouse
0
TRPV1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Retracted Publication
Langues
eng
Sous-ensembles de citation
IM
Pagination
1405-1417Commentaires et corrections
Type : RetractionIn
Informations de copyright
© 2022. The Author(s).
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