دورية أكاديمية
Palbociclib-Induced Cellular Senescence Is Modulated by the mTOR Complex 1 and Autophagy
| العنوان: | Palbociclib-Induced Cellular Senescence Is Modulated by the mTOR Complex 1 and Autophagy |
|---|---|
| المؤلفون: | Angel Cayo, Whitney Venturini, Danitza Rebolledo-Mira, Rodrigo Moore-Carrasco, Andrés A. Herrada, Estefanía Nova-Lamperti, Claudio Valenzuela, Nelson E. Brown |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 11, p 9284 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | senescence, cancer, mTORC1, autophagy, palbociclib, senescence-associated secretory phenotype, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Despite 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/11/9284; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms24119284 |
| URL الوصول: | https://doaj.org/article/9563503ffa3e498d91b2483f6abb91d6 |
| رقم الأكسشن: | edsdoj.9563503ffa3e498d91b2483f6abb91d6 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
|---|---|
| DOI: | 10.3390/ijms24119284 |