PAK5 Promotes Esophageal Squamous Cell Carcinoma Progression Revealed by Transcriptomic Profiling

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related mortality globally, particularly in Asia. Due to the lack of early symptoms, most patients are diagnosed at advanced stages, limiting treatment efficacy and worsening prognosis. Understanding the mechanisms underlying ESCC and identifying biomarkers or therapeutic targets are crucial for improving patient outcomes. P21-activated protein kinase 5 (PAK5), a member of the mitogen-activated protein kinase family, has been implicated in various malignancies by regulating cell cycle, migration, and invasion. However, its role in ESCC remains unclear. This study assessed PAK5 expression in ESCC tissues and adjacent normal tissues using immunohistochemistry and performed Kaplan-Meier survival analysis to evaluate the association between PAK5 and prognosis. ESCC cell models with PAK5 overexpression and knockdown were established, and functional assays, including CCK-8, colony formation, and Transwell assays, were conducted. Furthermore, mRNA sequencing was performed to identify downstream targets and signaling pathways regulated by PAK5. These results showed that PAK5 expression was significantly elevated in ESCC tissues compared with normal tissues and was associated with poor prognosis. Functional assays revealed that PAK5 promoted ESCC cell proliferation, colony formation, migration, and invasion, while transcriptomic analysis highlighted GAREM1 as a key downstream effector. These findings indicate that PAK5 contributes to ESCC progression and may serve as a prognostic biomarker and therapeutic target.