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dc.contributor.authorAlza, Lía
dc.contributor.authorVisa Pretel, Anna
dc.contributor.authorHerreros Danés, Judit
dc.contributor.authorCantí Nicolás, Carles
dc.description.abstractIn the strongly polarized membranes of excitable cells, activation of T-type Ca2+ channels (TTCCs) by weak depolarizing stimuli allows the influx of Ca2+ which further amplifies membrane depolarization, thus 'recruiting' higher threshold voltage-gated channels to promote action potential firing. Nonetheless, TTCCs perform other functions in the plasma membrane of both excitable and non-excitable cells, in which they regulate a number of biochemical pathways relevant for cell cycle and cell fate. Furthermore, data obtained in the last 20 years have shown the involvement of TTCCs in tumor biology, designating them as promising chemotherapeutic targets. However, their activity in the steadily-depolarized membranes of cancer cells, in which most voltage-gated channels are in the inactivated (nonconducting) state, is counter-intuitive. Here we discuss that in cancer cells weak hyperpolarizing stimuli increase the fraction of open TTCCs which, in association with Ca2+-dependent K+ channels, may critically boost membrane hyperpolarization and driving force for Ca2+ entry through different voltage-independent Ca2+ channels. Available evidence also shows that TTCCs participate in positive feedback circuits with signaling effectors, which may warrant a switch-like activation of pro-proliferative and pro-survival pathways in spite of their low availability. Unravelling TTCC modus operandi in the context of non-excitable membranes may facilitate the development of novel anticancer approaches.
dc.description.sponsorshipThis work was funded by grants from the Spanish Ministry of Science and Innovation/FEDER “Una manera de hacer Europa” (Retos Program, No. RTI2018-094739-B-I00 to JH & CC) and Fundacio La Marató de TV3 (No. 235/C/2019 to CC). LA is a recipient of an FI-AGAUR predoctoral fellowship. AV was funded by La Marató de TV3.
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094739-B-I00/ES/NUEVOS MECANISMOS DE DESREGULACION DE LA SEÑALIZACION POR CALCIO CONTRA EL GLIOBLASTOMA/
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofCell Calcium, 2022, vol. 105, p. 102610
dc.rightscc-by-nc-nd (c) authors, 2022
dc.subjectCalcium signaling pathways
dc.subjectCalcium-activated potassium channels
dc.subjectCancer cells
dc.subjectFeedback loops
dc.subjectMembrane potential
dc.subjectT-type calcium channels
dc.titleT-type channels in cancer cells: Driving in reverse

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cc-by-nc-nd (c) authors, 2022
Except where otherwise noted, this item's license is described as cc-by-nc-nd (c) authors, 2022