Hepatic Tumor Cell Morphology Plasticity under Physical Constraints in 3D Cultures Driven by YAP–mTOR Axis

Frtús, A.; Smolková, B.; Uzhytchak, M.; Lunova, M.; Jirsa, M.; Hof, M.; Jurkiewicz, P.; Lozinsky, V.I.; Wolfová, L.; Petrenko, Y.; Kubinová, Š.; Dejneka, A.; Lunov, O.

Авторы: Frtús Adam, Smolková Barbora, Uzhytchak Mariia, Lunova Mariia, Jirsa Milan, Hof Martin, Jurkiewicz Piotr, Lozinsky Vladimir I., Wolfová Lucie, Petrenko Yuriy, Kubinová Šárka, Dejneka Alexandr, Lunov Oleg
Журнал: Pharmaceuticals
Том: 13
Номер: 12
Год издания: 2020
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 1
Последняя страница: 25
Номер статьи: 430
DOI: 10.3390/ph13120430
Аннотация: Recent studies undoubtedly show that the mammalian target of rapamycin (mTOR) andthe Hippo–Yes-associated protein 1 (YAP) pathways are important mediators of mechanical cues.The crosstalk between these pathways as well as de-regulation of their signaling has been implicated inmultiple tumor types, including liver tumors. Additionally, physical cues from 3D microenvironmentshave been identified to alter gene expression and differentiation of different cell lineages. However,it remains incompletely understood how physical constraints originated in 3D cultures affect cellplasticity and what the key mediators are of such process. In this work, we use collagen scaffolds as amodel of a soft 3D microenvironment to alter cellular size and study the mechanotransduction thatregulates that process. We show that the YAP-mTOR axis is a downstream effector of 3D cellularculture-driven mechanotransduction. Indeed, we found that cell mechanics, dictated by the physicalconstraints of 3D collagen scaffolds, profoundly affect cellular proliferation in a YAP–mTOR-mediatedmanner. Functionally, the YAP–mTOR connection is key to mediate cell plasticity in hepatic tumorcell lines. These findings expand the role of YAP–mTOR-driven mechanotransduction to the controlhepatic tumor cellular responses under physical constraints in 3D cultures. We suggest a tentativemechanism, which coordinates signaling rewiring with cytoplasmic restructuring during cell growthin 3D microenvironments.
Добавил в систему: Лозинский Владимир Иосифович

	ИСТИНА	Войти в систему Регистрация
	ИСТИНА ЦЭМИ РАН
	Главная Поиск Статистика О проекте Помощь

ИСТИНА

ИСТИНА ЦЭМИ РАН

Hepatic Tumor Cell Morphology Plasticity under Physical Constraints in 3D Cultures Driven by YAP–mTOR Axisстатья

Прикрепленные файлы