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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• p21-activated kinase 5 (PAK5) overexpression is linked to tumor progression.
• The specific role of PAK5 in lung squamous cell carcinomas (LUSC) and its targets remain unclear.

Purpose of the Study:

• To investigate the role of PAK5 in LUSC progression and its effect on cancer stem cell phenotypes.
• To identify downstream targets of PAK5 in LUSC.

Main Methods:

• Utilized TCGA data for PAK5 expression analysis in LUSC.
• Employed RT-PCR, flow cytometry, and oncosphere assays to assess stem-like phenotypes.
• Used co-immunoprecipitation, western blotting, and immunofluorescence to identify SOX2 as a PAK5 effector.
• Established xenograft models to evaluate PAK5's role in tumor growth and metastasis.

Main Results:

• PAK5 is significantly overexpressed in LUSC tissues.
• PAK5 absence reduces LUSC cell self-renewal by decreasing SOX2 expression and phosphorylation.
• Knockdown or inhibition of PAK5 suppressed tumor growth and metastasis in vivo.
• SOX2 was identified as a novel downstream effector of PAK5.

Conclusions:

• PAK5 overexpression drives the cancer stem cell-like phenotype in LUSC through SOX2 phosphorylation.
• Targeting PAK5 presents a potential therapeutic strategy for SOX2-positive LUSC.