Overexpressed transient receptor potential vanilloid 1 (TRPV1) in lung adenocarcinoma harbours a new opportunity for therapeutic targeting

Nie, Yichu, Feng, Fenglan, Luo, Wei, Sanders, Andrew J. ORCID: 0000-0002-7997-5286, Zhang, Yidi, Liang, Jiaming, Chen, Cheng, Feng, Weineng, Gu, Weiquan, Liao, Weiping, Wang, Wei, Chen, Jinfeng, Zhang, Lijian, Jiang, Wen G. and Li, Jin (2022) Overexpressed transient receptor potential vanilloid 1 (TRPV1) in lung adenocarcinoma harbours a new opportunity for therapeutic targeting. Cancer Gene Therapy. doi:10.1038/s41417-022-00459-0

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Text 11541 Sanders, Nie, Feng, Luo, Zhang, Liang, Chen, Feng, Gu, Liao, Wang, Chen, Zhang, Jiang, Li (2022) Overexpressed transient receptor potential vanilloid 1 (TRPV1) in lung adenocarcinoma harbours a new opportunity for.pdf - Published Version Available under License Creative Commons Attribution 4.0. Download (7MB) | Preview

Abstract

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.

Item Type:	Article
Article Type:	Article
Uncontrolled Keywords:	Lung cancer; Lung adenocarcinoma; LUAD; Transient receptor potential vanilloid 1; TRPV1
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Schools and Research Institutes > School of Education and Science
Research Priority Areas:	Place, Environment and Community
Depositing User:	Andy Sanders
Date Deposited:	06 Sep 2022 10:22
Last Modified:	31 Aug 2023 08:57
URI:	https://eprints.glos.ac.uk/id/eprint/11541

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