Emerging role of transient receptor potential (TRP) channels in cancer progression

Abstract

Transient receptor potential (TRP) channels comprise a diverse family of ion channels, the majority of which are calcium permeable and show sophisticated regulatory patterns in response to various environmental cues. Early studies led to the recognition of TRP channels as environmental and chemical sensors. Later studies revealed that TRP channels mediated the regulation of intracellular calcium. Mutations in TRP channel genes result in abnormal regulation of TRP channel function or expression, and interfere with normal spatial and temporal patterns of intracellular local Ca 2+ distribution. The resulting dysregulation of multiple downstream effectors, depending on Ca 2+ homeostasis, is associated with hallmarks of cancer pathophysiology, including enhanced proliferation, survival and invasion of cancer cells. These findings indicate that TRP channels affect multiple events that control cellular fate and play a key role in cancer progression. This review discusses the accumulating evidence supporting the role of TRP channels in tumorigenesis, with emphasis on prostate cancer. [BMB Reports 2020; 53(3): 125-132]

TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer

“…In recent years, the involvement of Ca 2+ -permeable channels in neoplastic diseases has been extensively investigated and a direct correlation between their dysregulation and cancer development has been shown ( Monteith et al, 2017 ). Among them, Transient Receptor Potential (TRP) channels have revealed an important involvement in the regulation of many signaling pathways associated with tumor progression ( Yang and Kim, 2020 ). One of the key features of TRP channels is their polymodal activation mechanism and their involvement in different signal transduction pathways.…”

“…Among them, MMP-2 and MMP-9 are considered the most important in metastasis, since they were often aberrantly expressed in tumors ( Jabłońska-trypuć et al, 2016 ). Both TRP channels and small GTPases have been implicated in increased tumor invasiveness through the induction of MMPs expression ( Betson and Braga, 2003 ; Yang and Kim, 2020 ). Indeed, TRPM2, TRPM7, TRPM8, TRPV2, and TRPC1 have shown to cause upregulation of MMP9 in a Ca 2+ -dependent manner in gastric, bladder, oral squamous, prostate and thyroid cancer cells respectively ( Monet et al, 2010 ; Okamoto et al, 2012 ; Asghar et al, 2015 ; Cao et al, 2016 ; Chen L. et al 2017 ; Chen Z. et al, 2017 ; Almasi et al, 2019 ).…”

Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

“…Lastly, TRPM7 is highly expressed in OC cells and tissues and its expression level is significantly associated with poor prognosis in patients with OC [189]. Silencing of TRPM7 with siRNA inhibited OC cells proliferation, migration, and invasion, through direct regulation of calcium influx that, in turn, modulates many signaling transduction pathways including Akt, Src, and p38 ( Figure 1) [190,191].…”

Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance

“…Thus, its cellular level is always subjected to tight regulations, mainly by the activity of three plasma membrane Ca 2+ channels, voltage-gated Ca 2+ channels, Orai-mediated store-operated channels, and transient receptor potential-mediated Ca 2+ channels. It has been revealed that disruption in the expression or function of these channels is often correlated with carcinogenesis and/or chemoresistance [119,120]. Hence, targeting their expression level or function may serve as an effective strategy to improve cancer treatment.…”