The STRIPAK Complex Regulates Response to Chemotherapy Through p21 and p27

Carmen Rodriguez-Cupello, Monica Dam, Laura Serini, Shan Wang, David Lindgren, Emelie Englund, Pontus Kjellman, Håkan Axelson, Alberto García Mariscal, Chris Madsen

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

4 Citeringar (SciVal)

Sammanfattning

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.
Originalspråkengelska
Artikelnummer146
TidskriftFrontiers in cell and developmental biology
Volym8
DOI
StatusPublished - 2020 mar 17

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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