RETRACTED ARTICLE: Overexpressed transient receptor potential vanilloid 1 (TRPV1) in lung adenocarcinoma harbours a new opportunity for therapeutic targeting

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.

A novel transient receptor potential C3/C6 selective activator induces the cellular uptake of antisense oligonucleotides

“…Suppression of ASO uptake in the presence of the TRPC channel-selective inhibitor SKF96365 suggests that Ca 2+ influx via TRPC is associated with ASO uptake. Moreover, SKF96365 abolished the ASO uptake increased by CBD, which is known to activate TRPVs and TRPA1 in A549 cells expressing TRPV1 and TRPA1, as well as TRPC3 and TRPC6 ( 53 , 54 ). In addition, ASO uptake was not affected by nifedipine, a selective blocker of L-type voltage dependent calcium channels, that are widely expressed in various cells as a major source of calcium entry ( 55 , 56 ).…”

TRP Channels in Tumoral Processes Mediated by Oxidative Stress and Inflammation

“…In lung adenocarcinoma, the expression of TRPA1 and TRPV1 were upregulated by the hypoxia-inducible factor 1α (HIF1α) nuclear accumulation, finally leading to cell proliferation. The study proposes that the signaling pathway TRPV1-Ca 2+ -nNOS-NO activates proliferation and metastasis in these tumoral cells [57]. In other instances, TRPV1 hinders cell proliferation.…”

Anti-cancer activity and mechanism of flurbiprofen organoselenium compound RY-1-92 in non-small cell lung cancer

“…The expression trend of p-AKT and TRPV1 protein is consistent, 29 and AKT can participate in the transport of TRPV1. 30 Although studies have shown that TRPV1 protein is highly expressed in lung cancer cells, 31 the specific regulatory relationship between TRPV1 and MAPK-related proteins and p-AKT proteins in NSCLC cells is still rarely reported.…”