Orai3: Oncochannel with therapeutic potential

Ion channels in particular Calcium (Ca2+) channels play a critical role in
physiology by regulating plethora of cellular processes ranging from cell
proliferation, differentiation, transcriptional regulation and programmed cell death.
One of the most ubiquitous and highly regulated cellular Ca2+ influx pathways is
Store Operated Calcium Entry (SOCE) mediated by Orai1-3 channels. Orai
channels are responsible for Ca2+ influx across the plasma membrane in
response to decrease in Endoplasmic Reticulum (ER) Ca2+ stores. STIM1/STIM2
proteins sense the reduction in ER Ca2+ levels and activate Orai channels for
restoring ER Ca2+ as well as for driving cellular functions. Although Orai1 is the
ubiquitous SOCE channel protein, Orai2 and Orai3 mediate SOCE in certain
specific tissues. Further, mammalian specific homolog Orai3 forms
heteromultimeric channel with Orai1 for constituting Arachidonic acid regulated
Ca2+ (ARC) channels or arachidonic acid metabolite Leukotriene C4 (LTC4)
regulated Ca2+ (LRC) channels. Earlier work by us and others has highlighted a
key role for Orai3 channel in different types of cancers. In this review, we
retrospect the evidence supporting Orai3 as an oncochannel. We have further
discussed the potential of therapeutically targeting Orai3 for better management
and treatment of certain specific cancer subtypes. Most importantly, we have
highlighted key outstanding questions in the field that demand urgent attention
and further studies. deep

Tanwar J, Arora S, Motiani R K (2020) Orai3: Oncochannel with therapeutic potential. Cell Calcium 2020 doi.org/10.1016/j.ceca.2020.102247.

For full article: https://www.sciencedirect.com/science/article/pii/S0143416020300890?via%3Dihub


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