PAK5 promotes the migration and invasion of cervical cancer cells by phosphorylating SATB1

被引:37
|
作者
Huo, Fu-Chun [1 ,2 ]
Pan, Yao-Jie [3 ]
Li, Tong-Tong [1 ]
Mou, Jie [4 ]
Pei, Dong-Sheng [1 ,2 ]
机构
[1] Xuzhou Med Univ, Dept Pathol, Xuzhou 221004, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Jiangsu Key Lab Biol Canc Therapy, Xuzhou 221002, Jiangsu, Peoples R China
[3] Southeast Univ, Affiliated Yancheng Hosp, Med Sch, Dept Oncol, Yancheng 224001, Peoples R China
[4] Xuzhou Med Univ, Sch Pharm, Xuzhou 221004, Jiangsu, Peoples R China
来源
CELL DEATH AND DIFFERENTIATION | 2019年 / 26卷 / 06期
基金
中国国家自然科学基金;
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; P21-ACTIVATED KINASE-5; PROGNOSTIC-SIGNIFICANCE; POOR SURVIVAL; EXPRESSION; PROLIFERATION; PROGRESSION; STATISTICS; REGULATOR; CHROMATIN;
D O I
10.1038/s41418-018-0178-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
p21-activated kinase 5 (PAK5) is involved in several oncogenic signaling pathways and its amplification or overexpression has been found in various types of cancer; however, the pathophysiologic role of PAK5 in cervical cancer (CC) remains elusive. This study aims to elucidate the effects of PAK5 on CC metastasis and its specific regulation mechanism. We performed western blotting and immunohistochemistry (IHC) analysis and found that the expression levels of PAK5 were significantly upregulated in CC cells and tissues. In addition, statistical analysis via IHC showed that increased PAK5 significantly correlated with CC progression. Mn2+-Phos-tag SDS-PAGE, western blotting, immunofluorescence and dual luciferase reporter assays were utilized to determine the involvement of SATB1 in PAK5-mediated epithelial-mesenchymal transition (EMT). We found that PAK5-mediated special AT-rich binding protein-1 (SATB1) phosphorylation on Ser47 initiated EMT cascade and promoted migration and invasion of CC cells. Furthermore, overexpression of PAK5 induced lung metastasis of CC cells in xenograft modes. Taken together, we conclude that PAK5 is a novel prognostic indicator and plays an important role in the CC metastasis.
引用
收藏
页码:994 / 1006
页数:13
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