ILKAP drives hepatocellular carcinoma progression by modulating PGAM1-mediated glycolytic reprogramming

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, necessitating novel therapeutic targets. This study explores the oncogenic role of integrin-linked kinase-associated phosphatase (ILKAP) in HCC and its underlying mechanisms. Database analyses (TCGA, UALCAN) revealed ILKAP overexpression in HCC, correlating with poor prognosis. Functional assays demonstrated that ILKAP knockdown significantly suppressed HCC cell proliferation and migration in vitro, while xenograft models confirmed its role in tumor growth in vivo. RNA sequencing identified 357 differentially expressed genes (DEGs), including 48 protein-coding DEGs, with glycolytic enzyme PGAM1 notably downregulated upon ILKAP silencing. ILKAP and PGAM1 expression were positively correlated in HCC tissues, and elevated PGAM1 levels were linked to worse survival. Notably, restoring PGAM1 in ILKAP-knockdown cells rescued proliferation and invasion, underscoring PGAM1’s critical role in ILKAP-mediated tumor progression. ILKAP depletion also reduced extracellular acidification rates and altered glycolysis-related gene expression, highlighting its role in metabolic reprogramming. These findings suggest that ILKAP drives HCC malignancy by modulating PGAM1 and glycolysis, providing a potential therapeutic target for HCC treatment. Further elucidation of the ILKAP-PGAM1 axis may offer new strategies for liver cancer management.

Keywords

ILKAP / PGAM1 / HCC / glycolysis

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