Abstract
Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.
Highlights
Transient receptor potential (TRP) family is a large superfamily of widely expressed ion channels, which mainly conduct cations, including Ca2+, Mg2+, and Na+
Transient receptor potential melastatin 4 (TRPM4) is a potential diagnostic marker for cancer progression, as a correlation between TRPM4 expression and worse diagnostic outcomes has been reported for breast cancer [39], diffuse large B cell lymphoma (DLBCL) [33], and prostate cancer (PCa) [34,103]
TRPM4 was suggested as a protective diagnostic marker for endometrial cancer [106]
Summary
Transient receptor potential (TRP) family is a large superfamily of widely expressed ion channels, which mainly conduct cations, including Ca2+ , Mg2+ , and Na+. Intracellular Ca2+ directly activates TRPM4, which conducts an influx of Na+ [4]. TRPM4 was shown to be voltage-dependent, as membrane potential strongly modulates its activity [11]. TRPM40 s broad expression patterns support its potential implications in the physiological. Biomolecules 2021, 11, 229 functions of different cells, tissues, and organs. TRPM4 has been linked to a range of physiological processes, many involving fundamental cellular functions. TRPM4 contributes to several cancer hallmark functions, such as cell migration, proliferation, and the epithelial to mesenchymal transition (EMT).
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