medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2022.05.3-17medgen-2177Research ArticleНАУЧНЫЙ ОБЗОРREVIEWЕ-кадгерин в опухолевой прогрессии рака желудкаЕ-cadherin in gastric cancer tumorigenesisНемцоваМ. В.NemtsovaM. V.nemtsova_m_v@mail.ruБуреИ. В.BureI. V.noemail@neicon.ruЗалетаевД. В.ZaletaevD. V.noemail@neicon.ruКузнецоваЕ. Б.KuznetsovaE. B.noemail@neicon.ruВетчинкинаЕ. А.VetchinkinaE. A.noemail@neicon.ruМолчановА. Д.MolchanovA. D.noemail@neicon.ruФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет); ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияI.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Research Centre for Medical GeneticsRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)Russian FederationФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian Federation202209122022215317Copyright © Немцова М.В., Буре И.В., Залетаев Д.В., Кузнецова Е.Б., Ветчинкина Е.А., Молчанов А.Д., 20222022Немцова М.В., Буре И.В., Залетаев Д.В., Кузнецова Е.Б., Ветчинкина Е.А., Молчанов А.Д.Nemtsova M.V., Bure I.V., Zaletaev D.V., Kuznetsova E.B., Vetchinkina E.A., Molchanov A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2177

В основе инвазии и метастазирования опухолевых клеток лежит эпителиально-мезенхимальный переход (ЭМП). При этом состоянии происходит потеря связи между эпителиальными клетками и появляется подвижный фенотип, характерный для мезенхимальных клеток. Важную роль в процессе ЭМП играет белок Е-кадгерин, который устанавливает и поддерживает межклеточные взаимодействия и позволяет эпителиальным клеткам формировать клеточный пласт. Частичная или полная потеря экспрессии E-кадгерина, происходящая при ЭМП, опосредована механизмами, которые блокируют экспрессию активаторов белка и связанных с ним транскрипционных факторов. Напротив, происходит гиперэкспрессия генов его блокаторов SNAIL1/2, ZEB, TWIST1, GRHL2, OVOL1/2 и PRRX1. E-кадгерин задействован в различных онкогенных сигнальных путях, таких как Wnt/β-catenin, Rho GTPase и EGF/EGFR, благодаря чему он способствует развитию многих опухолей, включая рак желудка (РЖ). Важнейшие компоненты эпигенетического контроля экспрессии генов при канцерогенезе - микроРНК и длинные некодирующие РНК - участвуют в регуляции функции Е-кадгерина. Они действуют непосредственно или опосредованно, через многочисленные факторы, контролирующие транскрипцию гена, и таким образом влияют на пролиферацию и метастазирование опухолевых клеток. Этот обзор посвящен роли E-кадгерина в опухолевой прогрессии, а также участию некодирующих РНК в механизмах его экспрессионного контроля при канцерогенезе желудка.

Epithelial-mesenchymal transition (EMT) is the basis of tumor invasion and metastasis. It is characterized by the loss of communication between epithelial cells, which lead to the appearance of a motile phenotype of mesenchymal cells. The E-cadherin protein plays an important role in the EMT process, establishing and maintaining intercellular interactions and allowing epithelial cells to form a cell layer. The partial or complete loss of E-cadherin expression that occurs during EMT is mediated by mechanisms that block the expression of activators of this protein and related transcription factors. In contrast, the inhibitors of E-cadherin SNAIL1/2, ZEB, TWIST1, GRHL2, OVOL1/2, and PRRX1 are overexpressed. E-cadherin is involved in various oncogenic signaling pathways such as Wnt/β-catenin, Rho GTPase and EGF/EGFR. Therefore it contributes to many tumors, including gastric cancer (GC). MicroRNAs and long noncoding RNAs as important epigenetic regulators of gene expression in carcinogenesis are also involved in the regulation of E-cadherin function. They act directly or indirectly, through multiple factors controlling gene transcription, and thus influence tumor cell proliferation and metastasis. This review is focused on the role of E-cadherin in tumor progression and the involvement of non-coding RNAs in the mechanisms controlling its expression in gastric carcinogenesis.

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The authors declare that there are no conflicts of interest present.