The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2021 Jun 16

PMID 34131404

Citations 46

Authors

Li Li

Cheng Chen

Chengyao Chiang

Tian Xiao

Yangchao Chen

Yongxiang Zhao

Duo Zheng

Affiliations

Soon will be listed here.

Abstract

The transient receptor potential cation channel subfamily V member 1 (TRPV1) is a transmembrane protein that can be activated by various physical and chemical stimuli and is associated with pain transduction. In recent years, TRPV1 was discovered to play essential roles in cancer tumorigenesis and development, as TRPV1 expression levels are altered in numerous cancer cell types. Several investigations have discovered direct associations between TRPV1 and cancer cell proliferation, cell death, and metastasis. Furthermore, about two dozen TRPV1 agonists/antagonists are under clinical trial, as TRPV1 is a potential drug target for treating various diseases. Hence, more researchers are focusing on the effects of TRPV1 agonists or antagonists on cancer tumorigenesis and development. However, both agonists and antagonists may reveal anti-cancer effects, and the effect may function via or be independent of TRPV1. In this review, we provide an overview of the impact of TRPV1 on cancer cell proliferation, cell death, and metastasis, as well as on cancer therapy and the tumor microenvironment, and consider the implications of using TRPV1 agonists and antagonists for future research and potential therapeutic approaches.

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References

Fonseca B, Correia-da-Silva G, Teixeira N . Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis. J Physiol Biochem. 2018; 74(2):261-272. DOI: 10.1007/s13105-018-0611-7. View

Li W, Lee Y, Kim J, Kang S, Kim S, Kim K . Transient receptor potential vanilloid-1 mediates heat-shock-induced matrix metalloproteinase-1 expression in human epidermal keratinocytes. J Invest Dermatol. 2007; 127(10):2328-35. DOI: 10.1038/sj.jid.5700880. View

Cavanaugh D, Chesler A, Jackson A, Sigal Y, Yamanaka H, Grant R . Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci. 2011; 31(13):5067-77. PMC: 3087977. DOI: 10.1523/JNEUROSCI.6451-10.2011. View

Prevarskaya N, Ouadid-Ahidouch H, Skryma R, Shuba Y . Remodelling of Ca2+ transport in cancer: how it contributes to cancer hallmarks?. Philos Trans R Soc Lond B Biol Sci. 2014; 369(1638):20130097. PMC: 3917351. DOI: 10.1098/rstb.2013.0097. View

Farfariello V, Liberati S, Morelli M, Tomassoni D, Santoni M, Nabissi M . Resiniferatoxin induces death of bladder cancer cells associated with mitochondrial dysfunction and reduces tumor growth in a xenograft mouse model. Chem Biol Interact. 2014; 224:128-35. DOI: 10.1016/j.cbi.2014.10.020. View

Kosar P, Naziroglu M, Ovey I, Cig B . Synergic Effects of Doxorubicin and Melatonin on Apoptosis and Mitochondrial Oxidative Stress in MCF-7 Breast Cancer Cells: Involvement of TRPV1 Channels. J Membr Biol. 2015; 249(1-2):129-40. DOI: 10.1007/s00232-015-9855-0. View

Villalobo A, Berchtold M . The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis. Int J Mol Sci. 2020; 21(3). PMC: 7037201. DOI: 10.3390/ijms21030765. View

So C, Milevskiy M, Monteith G . Transient receptor potential cation channel subfamily V and breast cancer. Lab Invest. 2019; 100(2):199-206. DOI: 10.1038/s41374-019-0348-0. View

Huang K, Ma K, Chang Y, Lo L, Jhap T, Su Y . Baicalein inhibits matrix metalloproteinase 1 expression via activation of TRPV1-Ca-ERK pathway in ultraviolet B-irradiated human dermal fibroblasts. Exp Dermatol. 2019; 28(5):568-575. DOI: 10.1111/exd.13912. View

10.

Kalogris C, Caprodossi S, Amantini C, Lambertucci F, Nabissi M, Morelli M . Expression of transient receptor potential vanilloid-1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters. Histopathology. 2010; 57(5):744-52. DOI: 10.1111/j.1365-2559.2010.03683.x. View

11.

Kark T, Bagi Z, Lizanecz E, Pasztor E, Erdei N, Czikora A . Tissue-specific regulation of microvascular diameter: opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1. Mol Pharmacol. 2008; 73(5):1405-12. DOI: 10.1124/mol.107.043323. View

12.

Nakanishi M, Morita Y, Hata K, Muragaki Y . Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells. Exp Cell Res. 2016; 345(2):180-9. DOI: 10.1016/j.yexcr.2016.06.006. View

13.

Amantini C, Ballarini P, Caprodossi S, Nabissi M, Morelli M, Lucciarini R . Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis. 2009; 30(8):1320-9. DOI: 10.1093/carcin/bgp138. View

14.

Chiang C, Zhang M, Wang D, Xiao T, Zhu L, Chen K . Therapeutic potential of targeting MKK3-p38 axis with Capsaicin for Nasopharyngeal Carcinoma. Theranostics. 2020; 10(17):7906-7920. PMC: 7359099. DOI: 10.7150/thno.45191. View

15.

Apte R, Chen D, Ferrara N . VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019; 176(6):1248-1264. PMC: 6410740. DOI: 10.1016/j.cell.2019.01.021. View

16.

Uslusoy F, Naziroglu M, Cig B . Inhibition of the TRPM2 and TRPV1 Channels through in Sciatic Nerve Injury-induced Rats Demonstrates their Key Role in Apoptosis and Mitochondrial Oxidative Stress of Sciatic Nerve and Dorsal Root Ganglion. Front Physiol. 2017; 8:335. PMC: 5449501. DOI: 10.3389/fphys.2017.00335. View

17.

Oh-Hora M, Rao A . Calcium signaling in lymphocytes. Curr Opin Immunol. 2008; 20(3):250-8. PMC: 2574011. DOI: 10.1016/j.coi.2008.04.004. View

18.

Zygmunt P, Petersson J, Andersson D, Chuang H, Sorgard M, Di Marzo V . Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 1999; 400(6743):452-7. DOI: 10.1038/22761. View

19.

Liu T, Wang G, Tao H, Yang Z, Wang Y, Meng Z . Capsaicin mediates caspases activation and induces apoptosis through P38 and JNK MAPK pathways in human renal carcinoma. BMC Cancer. 2016; 16(1):790. PMC: 5059898. DOI: 10.1186/s12885-016-2831-y. View

20.

Weber L, Al-Refae K, Wolk G, Bonatz G, Altmuller J, Becker C . Expression and functionality of TRPV1 in breast cancer cells. Breast Cancer (Dove Med Press). 2016; 8:243-252. PMC: 5167528. DOI: 10.2147/BCTT.S121610. View