Oncogenic and Anti-Oncogenic Effects of Transient Receptor Potential Channels

Abstract

Transient Receptor Potential (TRP) channels affect several inflammatory and neoplastic conditions. About thirty TRPs have been identified to date and divided into seven families: TRPC (Canonical), TRPV (Vanilloid), TRPM (Melastatin), TRPML (Mucolipin), TRPP (Polycystin), and TRPA (Ankyrin transmembrane protein) and TRPN (NomPClike). Among these, the TRPC, TRPM, and TRPV families have been mainly correlated with malignant growth and progression. The aim of this review is to summarize data reported so far on the expression and functional role of TRP channels in different types of cancers. TRP channels have been recently implicated in the triggering of enhanced proliferation, aberrant differentiation, and resistance to apoptotic cell death, leading to uncontrolled tumor growth and progression. Depending on cancer stage, up and down-regulation of TRP mRNAs and protein expression have been reported. These changes have been shown to exhibit cancer promoting (oncogenic) or inhibiting/delaying (tumor suppressor) effects. We are only at the beginning, and more detailed study on the physiopathologic role of TRP channels is required to understand how the deregulation of TRP channel expression and function contributes to tumor development and progression. It is hoped that greater knowledge about TRP biology will enable future development of new chemotherapeutic agents for specific TRP targets, and the use of TRP channels as evaluable markers in diagnostic and/or prognostic analysis.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…In addition, multiple TRP channels are implicated in skin (Valdes-Rodriguez et al, 2013) and bladder (Charrua et al, 2010;Avelino et al, 2013) disorders as well as cancer Liberati et al, 2013). Taking these multifaceted and sometimes overlapping roles of TRP channels in a disease into consideration, targeting a single TRP channel might provide an insufficient effect because it may address only limited aspects of the disease.…”

“…Although no clear picture has yet emerged, there is increasing evidence that certain TRP channels may play opposing roles (oncogenic versus tumor suppressor) during carcinogenesis (reviewed in Prevarskaya et al, 2010;Lehen'kyi and Prevarskaya, 2011;Liberati et al, 2013;Morelli et al, 2013). To resolve some of the discrepancies in the literature, one might even postulate that this effect is cell type dependent; that is, a TRP channel that is oncogenic in one cell type may be conversely tumor suppressor in another.…”

“…Given the broad expression of TRP channels in normal tissues, the finding of altered TRP channel expression (including TRPV1, TRPV2, TRPV6, TRPC3, TRPC5, TRPC6, TRPM1-TRPM4, TRPM7, and TRPM8) in various cancers was hardly unexpected (reviewed in Prevarskaya et al, 2010;Lehen'kyi and Prevarskaya, 2011;Liberati et al, 2013;Morelli et al, 2013). For most TRP channels and cancers, it is unclear whether the observed changes are therapeutically relevant (i.e., involved in the proliferation and migration of tumor cells and/or in their resistance to chemotherapeutic agents) or simply an epiphenomenon of cancer progression.…”

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

“…For example, it has been shown that the endocannabinoids exert their apoptotic effect by binding to TRPV1, a non-selective cation channel targeted by capsaicin, the active component of hot chilli peppers (Smart & Jerman, 2000). However, the precise role of this receptor in cannabinoid signalling is still unclear and this uncertainty extends into the cancer field where its potential role in cancer biology (proliferation and migration of cancer cells) and cancer 8 pharmacology (resistance to chemotherapeutic agents) needs further investigation (Lehen'kyi et al, 2011;Liberati et al, 2013). Evidence also exists supporting a role for peroxisome proliferatoractivated receptors (PPARs) in the actions of cannabinoids (Sun et al, 2007).…”

The Effect of Arvanil on Prostate Cancer Cells Studied by Whole Cell High Resolution Magic Angle Spinning NMR

“…The Transient Receptor Potential cation channel subfamily V member 1 (TRPV1) has recently gained attention as a potential target for the development of novel antineoplastic agents [17][18][19][20]. It has been reported that the TRPV1 agonists have effective antiproliferative effects in studies using human breast, prostate, pancreatic, osteosarcoma, and gastric cancer cells lines [21][22][23][24][25].…”