Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?

Summary. The ORAI family of ion channel-forming proteins in mammals includes three members, ORAI1, ORAI2 and ORAI3, encoded by homologous genes. Of these proteins the ORAI1 one received major attention as plasma membrane constituent of store-operated calcium entry (SOCE) in non-exc...

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Datum:2023
1. Verfasser: Shuba, Ya.M.
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Sprache:English
Veröffentlicht: PH Akademperiodyka 2023
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Online Zugang:https://exp-oncology.com.ua/index.php/Exp/article/view/2019-3-9
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Experimental Oncology
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record_format ojs
institution Experimental Oncology
baseUrl_str
datestamp_date 2023-10-11T16:41:40Z
collection OJS
language English
topic apoptosis
cancer
invasion
migration
ORAI1
ORAI2
ORAI3
proliferation
store-operated calcium entry
spellingShingle apoptosis
cancer
invasion
migration
ORAI1
ORAI2
ORAI3
proliferation
store-operated calcium entry
Shuba, Ya.M.
Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?
topic_facet apoptosis
cancer
invasion
migration
ORAI1
ORAI2
ORAI3
proliferation
store-operated calcium entry
apoptosis
cancer
invasion
migration
ORAI1
ORAI2
ORAI3
proliferation
store-operated calcium entry
format Article
author Shuba, Ya.M.
author_facet Shuba, Ya.M.
author_sort Shuba, Ya.M.
title Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?
title_short Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?
title_full Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?
title_fullStr Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?
title_full_unstemmed Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?
title_sort ca2+ channel-forming orai proteins: cancer foes or cancer allies?
title_alt Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies?
description Summary. The ORAI family of ion channel-forming proteins in mammals includes three members, ORAI1, ORAI2 and ORAI3, encoded by homologous genes. Of these proteins the ORAI1 one received major attention as plasma membrane constituent of store-operated calcium entry (SOCE) in non-excitable cells. The functional significance of two other proteins, ORAI2 and ORAI3, is much less defined, although both of them participate to various extends in cell-specific modulation of SOCE as well as in supporting some of the store-independent calcium entry mechanisms. Calcium signaling becomes remodeled in cancer to promote cancer hallmarks — enhanced proliferation, resistance to apoptosis, motility and metastasizing. Although such remodeling commonly involves rearrangements of the whole molecular Ca2+-handling toolkit of the cell (Ca2+ pumps and transporters, Ca2+-binding and storage proteins, Ca2+ entry and release channels, Ca2+-dependent effectors), Ca2+ entry through Orai-based channels is especially important, as its dysregulation may contribute to several cancer hallmarks. The latter depend on the type of Ca2+-permeable channel formed by ORAI-proteins, spatiotemporal characteristics of Ca2+ signal that this channel contributes to, and the type Ca2+-dependent effector(s) targeted by this signal, all of which may be cancer-specific. By participating in global Ca2+ entry, ORAI-based SOCE may also contribute to cytosolic Ca2+ overload of cancer cells thereby playing pro-apoptotic, antineoplastic roles which can potentially be exploited for cancer treatment. This mini review examines various aspects of ORAI proteins in malignant transformation.
publisher PH Akademperiodyka
publishDate 2023
url https://exp-oncology.com.ua/index.php/Exp/article/view/2019-3-9
work_keys_str_mv AT shubayam ca2channelformingoraiproteinscancerfoesorcancerallies
first_indexed 2025-07-17T12:16:52Z
last_indexed 2025-07-17T12:16:52Z
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spelling oai:ojs2.ex.aqua-time.com.ua:article-2362023-10-11T16:41:40Z Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies? Ca2+ channel-forming ORAI proteins: cancer foes or cancer allies? Shuba, Ya.M. apoptosis, cancer, invasion, migration, ORAI1, ORAI2, ORAI3, proliferation, store-operated calcium entry apoptosis, cancer, invasion, migration, ORAI1, ORAI2, ORAI3, proliferation, store-operated calcium entry Summary. The ORAI family of ion channel-forming proteins in mammals includes three members, ORAI1, ORAI2 and ORAI3, encoded by homologous genes. Of these proteins the ORAI1 one received major attention as plasma membrane constituent of store-operated calcium entry (SOCE) in non-excitable cells. The functional significance of two other proteins, ORAI2 and ORAI3, is much less defined, although both of them participate to various extends in cell-specific modulation of SOCE as well as in supporting some of the store-independent calcium entry mechanisms. Calcium signaling becomes remodeled in cancer to promote cancer hallmarks — enhanced proliferation, resistance to apoptosis, motility and metastasizing. Although such remodeling commonly involves rearrangements of the whole molecular Ca2+-handling toolkit of the cell (Ca2+ pumps and transporters, Ca2+-binding and storage proteins, Ca2+ entry and release channels, Ca2+-dependent effectors), Ca2+ entry through Orai-based channels is especially important, as its dysregulation may contribute to several cancer hallmarks. The latter depend on the type of Ca2+-permeable channel formed by ORAI-proteins, spatiotemporal characteristics of Ca2+ signal that this channel contributes to, and the type Ca2+-dependent effector(s) targeted by this signal, all of which may be cancer-specific. By participating in global Ca2+ entry, ORAI-based SOCE may also contribute to cytosolic Ca2+ overload of cancer cells thereby playing pro-apoptotic, antineoplastic roles which can potentially be exploited for cancer treatment. This mini review examines various aspects of ORAI proteins in malignant transformation. Summary. The ORAI family of ion channel-forming proteins in mammals includes three members, ORAI1, ORAI2 and ORAI3, encoded by homologous genes. Of these proteins the ORAI1 one received major attention as plasma membrane constituent of store-operated calcium entry (SOCE) in non-excitable cells. The functional significance of two other proteins, ORAI2 and ORAI3, is much less defined, although both of them participate to various extends in cell-specific modulation of SOCE as well as in supporting some of the store-independent calcium entry mechanisms. Calcium signaling becomes remodeled in cancer to promote cancer hallmarks — enhanced proliferation, resistance to apoptosis, motility and metastasizing. Although such remodeling commonly involves rearrangements of the whole molecular Ca2+-handling toolkit of the cell (Ca2+ pumps and transporters, Ca2+-binding and storage proteins, Ca2+ entry and release channels, Ca2+-dependent effectors), Ca2+ entry through Orai-based channels is especially important, as its dysregulation may contribute to several cancer hallmarks. The latter depend on the type of Ca2+-permeable channel formed by ORAI-proteins, spatiotemporal characteristics of Ca2+ signal that this channel contributes to, and the type Ca2+-dependent effector(s) targeted by this signal, all of which may be cancer-specific. By participating in global Ca2+ entry, ORAI-based SOCE may also contribute to cytosolic Ca2+ overload of cancer cells thereby playing pro-apoptotic, antineoplastic roles which can potentially be exploited for cancer treatment. This mini review examines various aspects of ORAI proteins in malignant transformation. PH Akademperiodyka 2023-06-04 Article Article application/pdf https://exp-oncology.com.ua/index.php/Exp/article/view/2019-3-9 10.32471/exp-oncology.2312-8852.vol-41-no-3.13473 Experimental Oncology; Vol. 41 No. 3 (2019): Experimental Oncology; 200-206 Експериментальна онкологія; Том 41 № 3 (2019): Експериментальна онкологія; 200-206 2312-8852 1812-9269 10.32471/exp-oncology.2312-8852.vol-41-no-3 en https://exp-oncology.com.ua/index.php/Exp/article/view/2019-3-9/2019-3-9 Copyright (c) 2023 Experimental Oncology https://creativecommons.org/licenses/by-nc/4.0/