TRP channels in cancer

Abstract

The progression of cells from a normal differentiated state in which rates of proliferation and apoptosis are balanced to a tumorigenic and metastatic state involves the accumulation of mutations in multiple key signalling proteins and the evolution and clonal selection of more aggressive cell phenotypes. These events are associated with changes in the expression of numerous other proteins. This process of tumorigenesis involves the altered expression of one or more TRP proteins, depending on the nature of the cancer. The most clearly described changes are those involving TRPM8, TRPV6 and TRPM1. Expression of TRPM8 is substantially increased in androgen-dependent prostate cancer cells, but is decreased in androgen independent and metastatic prostate cancer. TRPM8 expression is regulated, in part, by androgens, most likely through androgen response elements in the TRPM8 promoter region. TRPM8 channels are involved in the regulation of cell proliferation and apoptosis. Expression of TRPV6 is also increased in prostate cancer and in a number of other cancers. In contrast to TRPM8, expression of TRPV6 is not directly regulated by androgens. TRPM1 is highly expressed in early stage melanomas but its expression declines with increases in the degree of aggressiveness of the melanoma. The expression of TRPV1, TRPC1, TRPC6, TRPM4, and TRPM5 is also increased in some cancers. The level of expression of TRPM8 and TRPV6 in prostate cancer, and of TRPM1 in melanomas, potentially provides a good prognostic marker for predicting the course of the cancer in individuals. The Drosophila melanogaster, TRPL, and the TRPV1 and TRPM8 proteins, have been used to try to develop strategies to selectively kill cancer cells by activating Ca(2+) and Na(+) entry, producing a sustained increase in the cytoplasmic concentration of these ions, and subsequent cell death by apoptosis and necrosis. TRPV1 is expressed in neurones involved in sensing cancer pain, and is a potential target for pharmacological inhibition of cancer pain in bone metastases, pancreatic cancer and most likely in other cancers. Further studies are required to assess which other TRP proteins are associated with the development and progression of cancer, what roles TRP proteins play in this process, and to develop further knowledge of TRP proteins as targets for pharmaceutical intervention and targeting in cancer.

Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines

“…The TRP members reported to be expressed abundantly in cancer cells include TRPV1, TRPV6, TRPM1, and TRPM8 (trp-p8) (2). Expression of TRPV1, a sensor of both noxious heat (>43˚C) and capsaicin, is increased in cancers of the prostate, colon, pancreas, and bladder, as well as in oral cancer (5).…”

“…In contrast, TRPM8 is activated by cooling (<26˚C) and by menthol (6,7). TRPM8 was originally cloned from human prostate (8), but is also expressed in many types of tumor tissues, such as breast, colon, lung, and skin (2). In prostate cancer cells, transition from the androgen-dependent state to the androgen-independent state causes loss of TRPM8 (9).…”

“…Its invasive ability gives it the highest incidence for malignancy of the oral cavity, characterized as local invasiveness and a propensity for dissemination to cervical lymph nodes (1). Some of the proteins involved in Ca 2+ homeostasis are known to be associated with tumor progression (2,3). In cancer cells, several members of the transient receptor potential (TRP)-channel family, which are Ca 2+ -and Na + -permeable channels, have been shown to play certain roles in tumor progression (3).…”

Ca2+ signaling mechanisms of cell survival and cell death: An introduction

“…An alternative strategy could be presented by targeting Ca 2+ signaling as a mediator of Ca 2+ -dependent cell death [55,56]. In this respect different types of Ca 2+ transporters [57], particularly IP 3 Rs [58] and some types of TRP channels [59] may play an important role. Different contributions in this Special Issue particularly by C. Distelhorst and M. Bootman, and by N. Prevarskaya and colleagues, deal with different aspects of cell death in cancer pathology.…”

Ion Channels as Promising Therapeutic Targets for Melanoma

“…anti-apoptotic activity of the P2X7 receptor). 3) Inversely, the expression of the channel belonging to transient receptor potential (TRP) cation channel subfamily M, TRPM1/Melastatin-1/MLSN-1, is decreased in melanomas according to melanoma aggressiveness and is useful as a prognostic marker for melanoma metastasis (see for review (Prevarskaya et al, 2007)). However, data and information relative to non-malignant melanocyte channel expression or function are scarce and have to be continued.…”