Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press87610.17650/1726-9776-2019-15-1-108-116REVIEWОБЗОРNotch signaling pathway: dual role in tumour progression and therapeutic opportunities for bladder cancerСигнальный путь Notch: двоякая роль в опухолевой прогрессии и терапевтические возможности при раке мочевого пузыряhttps://orcid.org/0000-0002-1974-3790NovikovaM. V.НовиковаМ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

Мария Вадимовна Новикова - лаборатория цитогенетики, лаборант-исследователь.

115478 Москва, Каширское шоссе, 24

mvnovikova94@mail.ruhttps://orcid.org/0000-0003-3100-2212KopninB. P.КопнинБ. П.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

Борис Павлович Копнин - лаборатория цитогенетики, доктор биологических наук, профессор, главнфый научный сотрудник.

115478 Москва, Каширское шоссе, 24

bkopnin@mail.ruhttps://orcid.org/0000-0002-2078-4274KopninP. B.КопнинП. Б.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

Павел Борисович Копнин - лаборатория цитогенетики, кандидат биологических наук, заведующий.

115478 Москва, Каширское шоссе, 24

pbkopnin@mail.ruResearch Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaНИИ канцерогенеза, ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России300320191511081162609201806112018https://oncourology.abvpress.ru/oncur/article/view/876

During cancer progression Notch signaling pathway and its components could demonstrate oncogenic and tumor-suppressive properties depending on tissue type and cellular microenvironment. However, until recently, very little was known about Notch role in bladder cancer (BC). According to recent studies it was revealed that loss of copy number and decreased expression of NOTCH1 is the hallmark of BC cell lines; and NOTCH1 activation in vitro reduces cell proliferation, suggesting that NOTCH1 acts as a tumor suppressor in BC. Furthermore, BC could be promoted by bladder-specific inactivation of a component of y-secretase complex, which is directly involved in Notch signaling, in vivo. By contrast, further studies have demonstrated that NOTCH2 acts as an oncogene which could promote cell proliferation and metastasis through induction of epithelial-to-mesenchymal transition and maintaining stemness. Studies indicating that NOTCH1 and NOTCH2 have opposite effects on BC progression could give rise to novel therapeutic approaches aimed at impact on Notch activity.

При опухолевой прогрессии сигнальный путь Notch и его компоненты могут проявлять как опухольсупрессирующие, так и онкогенные свойства в зависимости от типа ткани и микроокружения. До недавнего времени крайне мало было известно о роли Notch в развитии рака мочевого пузыря (РМП). По данным последних исследований было выявлено, что потеря копии и снижение экспрессии гена NOTCH1 характерны для клеточных линий РМП, а активация сигнального пути Notch1 снижает клеточную пролиферацию in vitro, что свидетельствует о его опухольсупрессирующей роли в прогрессировании РМП. Более того, РМП может быть индуцирован тканеспецифичной инактивацией одного из компонентов комплекса у-секретазы, принимающего непосредственное участие в запуске сигнального каскада Notch, in vivo. Однако результаты дальнейших исследований показали, что NOTCH2 является онкогеном, стимулирующим пролиферацию и метастазирование через индукцию эпителиально-мезенхимального перехода и поддержание фенотипа опухолевых стволовых клеток. Полученные данные, указывающие на противоположность свойств NOTCH1 и NOTCH2 в опухолевой прогрессии РМП, могут лечь в основу новых терапевтических подходов, связанных с воздействием на активность сигнального пути Notch.

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