Show simple item record

dc.contributor.authorCayo, Angel
dc.contributor.authorVenturini, Whitney
dc.contributor.authorRebolledo-Mira, Danitza
dc.contributor.authorMoore-Carrasco, Rodrigo
dc.contributor.authorHerrada, Andrés A.
dc.contributor.authorNova-Lamperti, Estefanía
dc.contributor.authorValenzuela, Claudio
dc.contributor.authorBrown, Nelson E.
dc.date.accessioned2024-04-10T00:07:56Z
dc.date.available2024-04-10T00:07:56Z
dc.date.issued2023
dc.identifier10.3390/ijms24119284
dc.identifier.issn16616596
dc.identifier.urihttps://hdl.handle.net/20.500.12728/10388
dc.description.abstractDespite not dividing, senescent cells acquire the ability to synthesize and secrete a plethora of bioactive molecules, a feature known as the senescence-associated secretory phenotype (SASP). In addition, senescent cells often upregulate autophagy, a catalytic process that improves cell viability in stress-challenged cells. Notably, this “senescence-related autophagy” can provide free amino acids for the activation of mTORC1 and the synthesis of SASP components. However, little is known about the functional status of mTORC1 in models of senescence induced by CDK4/6 inhibitors (e.g., Palbociclib), or the effects that the inhibition of mTORC1 or the combined inhibition of mTORC1 and autophagy have on senescence and the SASP. Herein, we examined the effects of mTORC1 inhibition, with or without concomitant autophagy inhibition, on Palbociclib-driven senescent AGS and MCF-7 cells. We also assessed the pro-tumorigenic effects of conditioned media from Palbociclib-driven senescent cells with the inhibition of mTORC1, or with the combined inhibition of mTORC1 and autophagy. We found that Palbociclib-driven senescent cells display a partially reduced activity of mTORC1 accompanied by increased levels of autophagy. Interestingly, further mTORC1 inhibition exacerbated the senescent phenotype, a phenomenon that was reversed upon autophagy inhibition. Finally, the SASP varied upon inhibiting mTORC1, or upon the combined inhibition of mTORC1 and autophagy, generating diverse responses in cell proliferation, invasion, and migration of non-senescent tumorigenic cells. Overall, variations in the SASP of Palbociclib-driven senescent cells with the concomitant inhibition of mTORC1 seem to depend on autophagy. © 2023 by the authors.es_ES
dc.description.sponsorshipPrograma de Investigación Asociativa en Cáncer Gástrico; Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT, (11201182); Universidad de Talca, UTALCAes_ES
dc.language.isoenes_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)es_ES
dc.subjectautophagyes_ES
dc.subjectcanceres_ES
dc.subjectmTORC1es_ES
dc.subjectpalbociclibes_ES
dc.subjectsenescencees_ES
dc.subjectsenescence-associated secretory phenotypees_ES
dc.titlePalbociclib-Induced Cellular Senescence Is Modulated by the mTOR Complex 1 and Autophagyes_ES
dc.typeArticlees_ES


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record