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The STRIPAK Complex Regulates Response to Chemotherapy Through p21 and p27

Rodriguez-Cupello, Carmen LU orcid ; Dam, Monica ; Serini, Laura ; Wang, Shan LU ; Lindgren, David LU ; Englund, Emelie LU ; Kjellman, Pontus LU ; Axelson, Håkan LU ; García Mariscal, Alberto LU and Madsen, Chris LU (2020) In Frontiers in Cell and Developmental Biology 8.
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... (More)
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. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Frontiers in Cell and Developmental Biology
volume
8
article number
146
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85082670188
  • pmid:32258031
ISSN
2296-634X
DOI
10.3389/fcell.2020.00146
language
English
LU publication?
yes
id
5264f5c9-b5c7-4cc0-9694-ddadd7e0a6a7
date added to LUP
2020-03-25 08:36:50
date last changed
2024-05-01 07:05:59
@article{5264f5c9-b5c7-4cc0-9694-ddadd7e0a6a7,
  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.}},
  author       = {{Rodriguez-Cupello, Carmen and Dam, Monica and Serini, Laura and Wang, Shan and Lindgren, David and Englund, Emelie and Kjellman, Pontus and Axelson, Håkan and García Mariscal, Alberto and Madsen, Chris}},
  issn         = {{2296-634X}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Cell and Developmental Biology}},
  title        = {{The STRIPAK Complex Regulates Response to Chemotherapy Through p21 and p27}},
  url          = {{http://dx.doi.org/10.3389/fcell.2020.00146}},
  doi          = {{10.3389/fcell.2020.00146}},
  volume       = {{8}},
  year         = {{2020}},
}