TRPM8-androgen receptor association within lipid rafts promotes prostate cancer cell migration

Grolez, Guillaume; Gordiendko, Dmitri V.; Clarisse, Manon; Hammadi, Mehdi; Desruelles, Emilie; Fromont, Gaëlle; Prevarskaya, Natalia; Slomianny, Christian; Gkika, Dimitra

doi:10.1038/s41419-019-1891-8

Cited by 42 publications

(55 citation statements)

References 49 publications

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“…This inhibition was produced by the activated AR interacting with the channel present within lipid-raft domains. Grolez et al (2019) proposed that the differences between their results and those from Asutkhar et al (2015) might be explained by the differences in the design of the experiments since the former study used lipid bilayers and cells lacking the AR receptor, as well as lower concentrations of testosterone. Thus, the elucidation of the precise molecular mechanism of androgen regulation of TRPM8 channels requires further investigation.…”

Section: Ion Channel Regulation By Androgensmentioning

confidence: 88%

“…The binding of testosterone was decreased by the presence of TRPM 8 agonists such as menthol (50 mM), icilin (10 mM), and M8-B (1 mM). However, Grolez et al (2019) showed that, testosterone (10 nM) inhibited the transient increase of the intracellular calcium concentration induced by icillin (10 mM) in the presence of the AR. These results suggest that at some concentrations, testosterone inhibits the activity of TRPM8 via an ARdependent mechanism.…”

Section: Ion Channel Regulation By Androgensmentioning

confidence: 96%

“…(B) Non-transcriptional pathways primarily involve the binding of the SH to a GPCR triggering second messenger pathways which may activate proteins targeting to ion channels. Alternatively, SH may bind to ion channels like TRPM8 and CatSper modulating its gating properties and enhancing calcium influx (Head et al, 1999;Asuthkar et al, 2015;Grolez et al, 2019). Changes in ion channel expression or activity produced by SH may in turn affect some cancer-associated processes, including cancer cell proliferation, migration, and invasion.…”

Section: Steroid Hormone Regulation Of Ion Channels As a Potential Opmentioning

confidence: 99%

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Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

2020

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Many ion channels are involved in tumor development, promoting cancer cell proliferation, migration, invasion, and survival. Accordingly, some of them have been suggested as tumor markers and novel targets for cancer therapy. Some sex steroid hormones (SSH), including estrogens and androgens, favor cancer progression. Meanwhile, other steroid hormones like vitamin D may have anticancer properties. SSH and vitamin D modulate the expression of a number of ion channels in cancer cells from hormone-sensitive tissues, including breast, ovary, prostate, and cervix. Moreover, rapid effects of SSH may be mediated by their direct action on membrane ion channels. Here, we reviewed the SSH and vitamin D regulation of ion channels involved in cancer, and analyzed the potential molecular pathways implicated. In addition, we described the potential clinical use of ion channels in cancer diagnosis and therapy, taking advantage of their regulation by SSH and vitamin D. Since SSH are considered risk factors for different types of cancer, and ion channels play important roles in tumor progression, the regulation of ion channels by SSH and vitamin D may represent a potential opportunity for early cancer diagnosis and therapeutic approaches in SSH and vitamin D sensitive tumors.

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Section: Ion Channel Regulation By Androgensmentioning

confidence: 88%

Section: Ion Channel Regulation By Androgensmentioning

confidence: 96%

Section: Steroid Hormone Regulation Of Ion Channels As a Potential Opmentioning

confidence: 99%

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Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

2020

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“…On the other hand, cholesterol-rich lipid rafts have been found to act as sites of intersection of androgen receptor (110 kDa) and AKT signaling in prostate cancer cells (177). Androgen receptor plays a major role in the pathogenesis of prostate cancer (178), and a functional interaction between transient receptor potential melastatin 8 (TRPM8) and androgen receptor in lipid rafts has been shown to promote cancer cell migration (179). (193).…”

Section: Estrogen Receptormentioning

confidence: 99%

Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

Mollinedo

Gajate

2020

Journal of Lipid Research

187

206

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Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

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“…Furthermore, the TRPM8 agonist WS12 encapsulated into lipid nanocapsules is able to impair cancer cell migration ability [51]. On the other hand, testosterone is able to inhibit TRPM8 activity [52]. Indeed, low (10 nM), but not high (100 nM), testosterone concentrations decrease TRPM8-mediated Ca 2+ influx, resulting in a significant increase in cell migration.…”

Section: Trpm Channels In Cancer Therapymentioning

confidence: 99%

Transient Receptor Potential Cation Channels in Cancer Therapy

et al. 2019

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In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

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TRPM8-androgen receptor association within lipid rafts promotes prostate cancer cell migration

Cited by 42 publications

References 49 publications

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

Transient Receptor Potential Cation Channels in Cancer Therapy

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