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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Acta Naturae</journal-id><journal-title-group><journal-title xml:lang="en">Acta Naturae</journal-title><trans-title-group xml:lang="ru"><trans-title>Acta Naturae</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2075-8251</issn><publisher><publisher-name xml:lang="en">Acta Naturae Ltd</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">27574</article-id><article-id pub-id-type="doi">10.32607/actanaturae.27574</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Store-operated calcium entry as an important mechanism of tumor adaptation to an aggressive microenvironment</article-title><trans-title-group xml:lang="ru"><trans-title>Депо-управляемый вход кальция – как важный механизм адаптации опухоли к агрессивному микроокружению</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Skopin</surname><given-names>A. Yu.</given-names></name><name xml:lang="ru"><surname>Скопин</surname><given-names>А. Ю.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>evkazn@incras.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kaznacheyeva</surname><given-names>E. V.</given-names></name><name xml:lang="ru"><surname>Казначеева</surname><given-names>Е. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>evkazn@incras.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Institute of Cytology, Russian Academy of Sciences</institution></aff><aff><institution xml:lang="ru">Институт цитологии РАН</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2025-10-14" publication-format="electronic"><day>14</day><month>10</month><year>2025</year></pub-date><volume>17</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>28</fpage><lpage>39</lpage><history><date date-type="received" iso-8601-date="2024-11-29"><day>29</day><month>11</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2025-04-22"><day>22</day><month>04</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Skopin A.Y., Kaznacheyeva E.V.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Скопин А.Ю., Казначеева Е.В.</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Skopin A.Y., Kaznacheyeva E.V.</copyright-holder><copyright-holder xml:lang="ru">Скопин А.Ю., Казначеева Е.В.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://actanaturae.ru/2075-8251/article/view/27574">https://actanaturae.ru/2075-8251/article/view/27574</self-uri><abstract xml:lang="en"><p>Calcium signaling ensures efficient cellular functioning; calcium homeostasis disruption leaves behind detrimental sequelae for the cell both under calcium excess and deficiency conditions. Malignant transformation is accompanied by significant alterations in the expression of the proteins critical for store-operated calcium entry, resulting in the dysregulation of calcium signaling. It is plausible that a remodeling of intracellular signal transduction pathways in cancer cells is required in order to accelerate metabolic processes, as well as fuel further tumor growth and invasion. Meanwhile, fine-tuning of calcium signaling is observed under both normal and pathological conditions. In this context, research into the changes accompanying signal transduction within the tumor microenvironment is a key aspect of the investigation of the role of calcium signaling in tumor development. Factors characteristic of the tumor microenvironment were shown to have a significant effect on the function of calcium channels and the proteins that regulate calcium signaling. Major, adverse microenvironmental factors, such as acidification, elevated levels of reactive oxygen species and hypoxia, have a bearing on the store-operated calcium entry. It is crucial to understand whether changes in the expression of the key SOCE components represent an adaptation to the microenvironment or a result of carcinogenesis.</p></abstract><trans-abstract xml:lang="ru"><p>Кальциевая сигнализация обеспечивает эффективное функционирование клетки, а нарушение баланса в системе кальциевого гомеостаза ведет к негативным последствиям для клетки в случае как избытка, так и недостатка кальция. При опухолевой трансформации наблюдается существенное изменение экспрессии белков, ключевых для депо-управляемого входа кальция, что приводит к нарушению процессов кальциевой сигнализации. Вполне вероятно, что перестройка внутренних сигнальных путей опухолевой клетки необходима для интенсификации метаболических процессов и дальнейшего роста и инвазии опухоли. Вместе с тем, тонкая настройка кальциевой сигнализации наблюдается как в норме, так и при патологии. В этой связи особое место в исследовании роли кальциевой сигнализации при развитии опухолевой трансформации занимает изучение перенастройки сигнализации в опухолевом окружении. Показано, что факторы, характерные для микроокружения опухоли, оказывают существенное влияние на работу кальциевых каналов и белков, регулирующих кальциевую сигнализацию. Основные негативные факторы микроокружения, такие как закисление, повышение уровня активных радикалов и гипоксия, влияют на депо-управляемый вход кальция. Весьма важно понять, являются ли изменения в экспрессии ключевых участников депо-управляемого входа кальция адаптацией к микроокружению или же следствием канцерогенеза.</p></trans-abstract><kwd-group xml:lang="en"><kwd>calcium</kwd><kwd>store-operated calcium entry</kwd><kwd>STIM</kwd><kwd>Orai</kwd><kwd>malignant transformation</kwd><kwd>tumor microenvironment</kwd><kwd>calcium signaling</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>кальций</kwd><kwd>депо-управляемый вход</kwd><kwd>STIM</kwd><kwd>Orai</kwd><kwd>опухолевая трансформация</kwd><kwd>микроокружение опухоли</kwd><kwd>кальциевая сигнализация</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="en">Ministry of Science and Higher Education of the Russian Federation</institution></institution-wrap><institution-wrap><institution xml:lang="ru">Министерство науки и высшего образования Российской Федерации</institution></institution-wrap></funding-source><award-id>075-15-2021-1075</award-id></award-group><award-group><funding-source><institution-wrap><institution xml:lang="en">Russian Science Foundation</institution></institution-wrap><institution-wrap><institution xml:lang="ru">Российский научный фонд</institution></institution-wrap></funding-source><award-id>23-44-00054</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Califano A., Alvarez M.J. // Nat. 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