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

Nie, Yochu, Feng, Fenglan, Luo, Wei, Sanders, Andrew J. ORCID: https://orcid.org/0000-0002-7997-5286, Zhang, Yidi, Liang, Jiaming, Chen, Cheng, Feng, Weineng, Gu, Weiquan, Liao, Weiping, Wang, Wei, Chen, Jifeng, Zhang, Lianjian, Jiang, Wen G. ORCID: https://orcid.org/0000-0002-3283-1111 and Li, Jin 2022. Overexpressed transient receptor potential vanilloid 1 (TRPV1) in lung adenocarcinoma harbours a new opportunity for therapeutic targeting [RETRACTED]. Cancer Gene Therapy 29 , pp. 1405-1417. 10.1038/s41417-022-00459-0

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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
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	The Editor-in-Chief has retracted this article. See Nie, Y., Feng, F., Luo, W. et al. Retraction Note: Overexpressed transient receptor potential vanilloid 1 (TRPV1) in lung adenocarcinoma harbours a new opportunity for therapeutic targeting. Cancer Gene Ther 30, 1583 (2023). https://doi.org/10.1038/s41417-023-00677-0
Publisher:	Springer Nature
ISSN:	0929-1903
Funders:	RealCan Fellowship (AJS) at Cardiff Universit. This study was supported by the project of Pearl River Nova Program of Guangzhou (No. 201806010008), the project of the International Postdoctoral Exchange Fellowship Program (No.20150075), the National Natural Science Foundation of China (81672270), the Natural Science Foundation of Guangdong Province, China (2020KZDZX1160), the Key Project of Guangzhou Science Technology and Innovation Committee (201707020042), the Autonomous Foundation of the State Key Laboratory of Respiratory Diseases (SKLRD-QN-201907, SKLRD2016ZJ017), the Opening Foundation of the State Key Laboratory of Respiratory Diseases (SKLRD-OP-201915).
Related URLs:	https://doi.org/10.1038/s41417-023-00677...
Date of First Compliant Deposit:	22 March 2022
Date of Acceptance:	9 March 2022
Last Modified:	11 Mar 2024 10:37
URI:	https://orca.cardiff.ac.uk/id/eprint/148312

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