Role of the TRP Channels in Pancreatic Ductal Adenocarcinoma Development and Progression

Abstract

The transient receptor potential channels (TRPs) have been related to several different physiologies that range from a role in sensory physiology (including thermo- and osmosensation) to a role in some pathologies like cancer. The great diversity of functions performed by these channels is represented by nine sub-families that constitute the TRP channel superfamily. From the mid-2000s, several reports have shown the potential role of the TRP channels in cancers of multiple origin. The pancreatic cancer is one of the deadliest cancers worldwide. Its prevalence is predicted to rise further. Disappointingly, the treatments currently used are ineffective. There is an urgency to find new ways to counter this disease and one of the answers may lie in the ion channels belonging to the superfamily of TRP channels. In this review, we analyse the existing knowledge on the role of TRP channels in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The functions of these channels in other cancers are also considered. This might be of interest for an extrapolation to the pancreatic cancer in an attempt to identify potential therapeutic interventions.

The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma

“…In conclusion, all of these results consistently point towards some family members being important players in the tumorigenic process: TRPM8 , TRPM7 , TRPV6 , and TRPA1 [ 11 ]. Only recently has a study using the gene set enrichment analysis (GSEA) shown that two members of the TRPC subfamily ( TRPC3 and TRPC7 ) possess clinical predictive value for PDAC.…”

The Emergence of TRP Channels Interactome as a Potential Therapeutic Target in Pancreatic Ductal Adenocarcinoma

“…Transient Receptor Potential (TRP) channels are a family of nonselective ion channels mediating various physiological functions in many cell types. These channels have recently been identified as critical regulators of pancreatic cancer cell proliferation, invasion, and metastasis [ 4 , 5 , 6 , 7 ]. Targeting TRP channels represents an exciting new strategy for inhibiting pancreatic cancer cell growth and survival.…”

“…Moreover, the development of effective treatment methods for pancreatic cancer has been hindered by the lack of understanding of the pathogenesis, partly due to the difficulty in studying human tissue samples. Despite this, scientific research on this topic has witnessed steady development in the past few years in understanding the molecular mechanisms that underlie TRP channel disturbance [ 4 , 5 , 6 , 7 ]. The focus is on exploring the pathogenesis of pancreatic cancer and its related pathways.…”

“…Several studies have shown that TRP channels are frequently overexpressed in pancreatic cancer cells, and their expression levels correlate with poor prognosis and increased tumor growth. Transient receptor potential vanilloid 1 (TRPV1) is a calcium-permeable ion channel gated by the pungent constituent of red chili pepper, capsaicin, and related chemicals from the group of vanilloids, as well as by noxious heat stimuli [ 4 , 5 , 6 , 7 ]. TRPV1 has been linked to promoting PDAC cell proliferation and migration.…”

Sensory Ion Channel Candidates Inform on the Clinical Course of Pancreatic Cancer and Present Potential Targets for Repurposing of FDA-Approved Agents

“…TRPs are discussed to be important mediators of pain and are under current investigation as targets for developing new pain medications [ 12 ]. In addition to the role of maintaining tissue homeostasis, some previous reports link malignant disease progression with responses of these channels including for PAAD [ 13 ]. However, to our knowledge the relevance of TRP from a translational viewpoint, interrogating NGS data of patient material and clinical course, has been not been assessed.…”