2. Academic Validation
  3. PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas

PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas

  • Exp Cell Res. 2020 Oct 15;395(2):112187. doi: 10.1016/j.yexcr.2020.112187.
Zinan Bao 1,  Wenxiang Ji 2,  Ying Yang 2,  Zhuo Chen 3,  Ziming Li 2,  Kaixuan Wang 2,  Tingting Lu 2,  Yongfeng Yu 2,  Weiliang Xia 4,  Shun Lu 5
Affiliations

Affiliations

  • 1 Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, West Huaihai Road 241, 20030, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Huashan Road 1954, 200030, Shanghai, China.
  • 2 Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, West Huaihai Road 241, 20030, Shanghai, China.
  • 3 School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Huashan Road 1954, 200030, Shanghai, China.
  • 4 School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Huashan Road 1954, 200030, Shanghai, China. Electronic address: wlxia@sjtu.edu.cn.
  • 5 Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, West Huaihai Road 241, 20030, Shanghai, China. Electronic address: shunlu@sjtu.edu.cn.
PMID: 32721391 DOI: 10.1016/j.yexcr.2020.112187
Abstract

Growing evidences suggest that the overexpression of p21-activated kinase 5 (PAK5) plays an important role in various tumor progression. However, the role of PAK5 and its downstream target gene(s) in lung squamous cell carcinomas (LUSC) are waiting to be elucidated. TCGA data were utilized to evaluate the expression levels of PAK5 in LUSC. We then explored the role of PAK5 in maintaining the stem-like phenotype of lung squamous Cancer cells through RT-PCR, flow cytometry, oncosphere-forming assay. In addition, co-immunoprecipitation, western blotting and immunofluorescence assays were used to determine SOX2 as a novel effector of PAK5. Xenograft models in nude mice were established to explore the roles of PAK5 in lung Cancer growth. In this study, we have shown that PAK5 is overexpressed in LUSC tissues. The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo. In xenograft models, knockdown or pharmacological inhibition of PAK5 suppressed the tumor growth and metastasis of lung squamous Cancer cells in vivo. Taken together, our findings suggest that the PAK5-mediated SOX2 phosphorylation promoted the Cancer stem cell-like phenotype of LUSC cells. PAK5 inhibition may be a promising target in the treatment of SOX2 positive lung squamous cell Cancer.

Keywords

Cancer stem cell; Lung squamous cell carcinomas; PAK5; Phosphorylation; SOX2.

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