Abstract

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.

Highlights

  • Sex steroid hormones (SSH) have been considered as a risk factor to develop a variety of human cancers, including those from breast, endometrium, ovary, cervix, colon, and prostate (Maxwell et al, 2009)

  • Many ion channels favor tumor progression in hormone-sensitive tissues, the immediate arising question is whether sex steroid hormones (SSH) may regulate the expression or activity of ion channels involved in cancer

  • Knockdown of TRPV5 in these cells inhibited cell proliferation, migration, and invasion induced by vitamin D receptor (VDR) knockdown. These results suggest that VDR acts as a tumor suppressor in renal cancer cells, and that this action includes the suppression of TRPV5 channel expression

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Summary

INTRODUCTION

Sex steroid hormones (SSH) have been considered as a risk factor to develop a variety of human cancers, including those from breast, endometrium, ovary, cervix, colon, and prostate (Maxwell et al, 2009). It has been proposed that such non-transcriptional actions are produced by hormone binding to either G-protein-coupled membrane receptors or the classical intracellular receptor types embedded into the cell membrane Examples of these types of receptors are the GPR30 receptor for estrogens (Meyer et al, 2011; Reslan and Khalil, 2012; Wang et al, 2014; Chen et al, 2019), variants of the ERa (Pietras and Márquez-Garbán, 2007; Adlanmerini et al, 2014; Arnal et al, 2017), or the calcium ion channel CatSper, which has a binding domain for prostaglandins and mediates progesterone-induced Ca2+ influx in human sperm (Strünker et al, 2011). Some examples of these effects in non-cancer cells are discussed

Cardiovascular System
Estrogenic Regulation of Ion Channels
Ion Channel Regulation by Androgens
Regulation of Ion Channels by Vitamin D and Calcitriol
Calcium influx and anchorageindependent growth
Findings
CONCLUDING REMARKS
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