A novel strategy for treating cancer: understanding the role of Ca2+ signaling from nociceptive TRP channels in regulating cancer progression

Abstract

Cancer is an aging-associated disease and caused by genomic instability that is driven by the accumulation of mutations and epimutations in the aging process. Although Ca2+ signaling, reactive oxygen species (ROS) accumulation, DNA damage response (DDR) and senescence inflammation response (SIR) are processed during genomic instability, the underlying mechanism for the cause of genomic instability and cancer development is still poorly understood and needs to be investigated. Nociceptive transient receptor potential (TRP) channels, which firstly respond to environmental stimuli, such as microbes, chemicals or physical injuries, potentiate regulation of the aging process by Ca2+ signaling. In this review, the authors provide an explanation of the dual role of nociceptive TRP channels in regulating cancer progression, initiating cancer progression by aging-induced genomic instability, and promoting malignancy by epigenetic regulation. Thus, therapeutically targeting nociceptive TRP channels seems to be a novel strategy for treating cancers.

TRPC7 facilitates cell growth and migration by regulating intracellular Ca2+ mobilization in lung adenocarcinoma cells

“…Calcium signals are central in the mechanisms underlying cancer cell proliferation, death and migration ( 1 ). Therefore, TRPC7 may promote cancer development and TRPC6 or other TRP channels cannot be excluded from roles in the regulation of cancer development through Ca 2+ /CaMKII/AKT and/or Ca 2+ /CaMKII/ERK axes ( 5 ). Furthermore, cell proliferation results of the present study only demonstrated the significance at Day 2 ( Fig.…”

“…6 ). There are an increasing number of TRP channels that have been reported to promote cancer development and Ca 2+ /CaMKII has emerged as a crucial signaling pathway in the modulation of cell proliferation, the cell cycle, invasion and metastasis, and therapy efficacy in cancer ( 5 ). For example, TRPV4 promotes oral squamous cell carcinoma cell proliferation via activation of the Ca 2+ /CaMKII/AKT axis ( 19 ) and TRPM7 mediates breast cancer cell migration and invasion via the CaMKII-dependent MAPK signaling pathway ( 20 ).…”

“…Furthermore, epigenetic mechanisms have been reported to promote the expression of TRP channels in cancer cells ( 5 ). Therefore, TRPC7 overexpression in lung adenocarcinoma cells may be involved in epigenetic mechanisms.…”

“…Recently, transient receptor potential (TRP) channels were reported to be associated with the development and progression of cancer ( 5 ). Ca 2+ signaling from nociceptive TRP channels controls cancer pathophysiology ( 6 ) and the therapeutic targeting of TRP channels provides a novel approach for the treatment of cancer.…”

A Chiral Nanocomplex for Multitarget Therapy to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits

“…[16,17] H 2 has emerged as a promising therapeutic option for oxidative stress-related diseases, including AD, [18,19] owing to its ability to attenuate ROS and inflammatory responses. [20] In recent years, the in situ photocatalytic H 2 production of semiconductor nanomaterials has garnered widespread attention. The underlying principle is that when a semiconductor absorbs photons, valence band electrons become excited to the conduction band, leaving behind holes (h + ).…”