The STRIPAK Complex Regulates Response to Chemotherapy Through p21 and p27

被引：12

作者：

Rodriguez-Cupello, Carmen ^{[1
]}

Dam, Monica ^{[1
]}

Serini, Laura ^{[1
]}

Wang, Shan ^{[1
]}

Lindgren, David ^{[1
]}

Englund, Emelie ^{[1
]}

Kjellman, Pontus ^{[1
]}

Axelson, Hakan ^{[1
]}

Garcia-Mariscal, Alberto ^{[1
]}

Madsen, Chris D. ^{[1
]}

机构：

[1] Lund Univ, Dept Lab Med, Div Translat Canc Res, Lund, Sweden

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2020年 / 8卷

基金：

瑞典研究理事会;

关键词：

breast cancer; STRIPAK; cell cycle; p21; p27; DNA damage response; chemotherapy; CELL-CYCLE; PHOSPHORYLATION; PROTEIN; PROLIFERATION; INSTABILITY; SENESCENCE; EXPRESSION; MIGRATION; COMPONENT; GENES;

D O I：

10.3389/fcell.2020.00146

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 p21(high)/gamma H2AX(low) 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.

引用

页数：14

共 50 条

[1] p21 in cancer: intricate networks and multiple activities [J].