The STRIPAK Complex Regulates Response to Chemotherapy Through p21 and p27.
Front Cell Dev Biol
; 8: 146, 2020.
Article
em En
| MEDLINE
| ID: mdl-32258031
ABSTRACT
The STRIPAK complex has been linked to a variety of biological processes taking place during embryogenesis and development, but its role in cancer has only just started to be defined. Here, we expand on previous work indicating a role for the scaffolding protein STRIP1 in cancer cell migration and metastasis. We show that cell cycle arrest and decreased proliferation are seen upon loss of STRIP1 in MDA-MB-231 cells due to the induction of cyclin dependent kinase inhibitors, including p21 and p27. We demonstrate that p21 and p27 induction is observed in a subpopulation of cells having low DNA damage response and that the p21high/γH2AXlow ratio within single cells can be rescued by depleting MST3&4 kinases. While the loss of STRIP1 decreases cell proliferation and tumor growth, cells treated with low dosage of chemotherapeutics in vitro paradoxically escape therapy-induced senescence and begin to proliferate after recovery. This corroborates with already known research on the dual role of p21 and indicates that STRIP1 also plays a contradictory role in breast cancer, suppressing tumor growth, but once treated with chemotherapeutics, allowing for possible recurrence and decreased patient survival.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Front Cell Dev Biol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Suécia