Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells
<p dir="ltr">Intracellular calcium (Ca<sup>2+</sup>) concentration ([Ca<sup>2+</sup>]i) is a key determinant of cell fate and is implicated in carcinogenesis. Membrane ion channels are structures through which ions enter or exit the cell, depending on the driv...
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| مؤلفون آخرون: | , , |
| منشور في: |
2020
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إضافة وسم
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| الملخص: | <p dir="ltr">Intracellular calcium (Ca<sup>2+</sup>) concentration ([Ca<sup>2+</sup>]i) is a key determinant of cell fate and is implicated in carcinogenesis. Membrane ion channels are structures through which ions enter or exit the cell, depending on the driving forces. The opening of transient receptor potential vanilloid 1 (TRPV1) ligand-gated ion channels facilitates transmembrane Ca<sup>2+</sup> and Na+ entry, which modifies the delicate balance between apoptotic and proliferative signaling pathways. Proliferation is upregulated through two mechanisms: (1) ATP binding to the G-protein-coupled receptor P2Y2, commencing a kinase signaling cascade that activates the serine-threonine kinase Akt, and (2) the transactivation of the epidermal growth factor receptor (EGFR), leading to a series of protein signals that activate the extracellular signal-regulated kinases (ERK) 1/2. The TRPV1-apoptosis pathway involves Ca<sup>2+</sup> influx and efflux between the cytosol, mitochondria, and endoplasmic reticulum (ER), the release of apoptosis-inducing factor (AIF) and cytochrome c from the mitochondria, caspase activation, and DNA fragmentation and condensation. While proliferative mechanisms are typically upregulated in cancerous tissues, shifting the balance to favor apoptosis could support anti-cancer therapies. TRPV1, through [Ca<sup>2+</sup>]i signaling, influences cancer cell fate; therefore, the modulation of the TRPV1-enforced proliferation–apoptosis balance is a promising avenue in developing anti-cancer therapies and overcoming cancer drug resistance. As such, this review characterizes and evaluates the role of TRPV1 in cell death and survival, in the interest of identifying mechanistic targets for drug discovery.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms21114177" target="_blank">https://dx.doi.org/10.3390/ijms21114177</a></p> |
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