PINK1 suppresses malignant phenotypes in esophageal squamous cell carcinoma

Abstract

Abstract Objective Esophageal squamous cell carcinoma (ESCC) is a common tumor characterized by a poor prognosis. PINK1 is strongly associated with tumorigenesis. However, the role of PINK1 in the progression of ESCC has not been elucidated. Methods The expression levels of PINK1 in tumor samples and corresponding normal tissues were evaluated using RNA-sequencing and gene expression array datasets. Pathway enrichment and immune infiltration analyses were performed to explore the role of PINK1 in ESCC development. Subsequently, cell counting kit-8, colony-forming assay, and Transwell assays were implemented to measure the proliferation and motility of ESCC cells. The glucose, ATP, pyruvate, and lactate concentrations were measured using suitable assay kits. Results PINK1 expression was significantly lower in ESCC samples across independent cohorts. In vitro assays demonstrated that PINK1 could inhibit the proliferation, migration, and invasive capabilities of ESCC cells. Furthermore, PINK1 could decrease intracellular glucose, lactic acid, pyruvic acid, and ATP levels in ESCC cells, whereas the glycolytic inhibitor 2-DG could abrogate its effect. Additionally, immunosuppressive-related gene sets were enriched in the PINK1 low-expression group. Immune infiltration analysis revealed that PINK1 expression was positively correlated with dendritic cells and T helper 1 cells within the tumor microenvironment. Conclusions PINK1 inhibits cell growth, movement, glycolysis, and immune activation in ESCC, making it a promising therapeutic target.

Keywords

• ESCC
• PINK1
• Proliferation
• Motility
• Glycolysis
• Immune activation