Choline kinase α interacts with epidermal growth factor receptor to activate the mitogen-activated protein kinase pathway and contributes to glioma tumorigenesis

Abstract Background: Glioma is a common malignant brain tumor with poor prognosis. Choline kinase α (CHKA) has been implicated in glioma progression, but its regulatory mechanisms remain unclear. Methods: Single-cell ribonucleic acid (RNA) sequencing was performed to assess the coexpression of CHKA and epidermal growth factor receptor (EGFR) in glioma subpopulations. Public datasets were analyzed to evaluate their clinical relevance, which was verified in a cohort from Ningxia Medical Hospital (November 2019–October 2024). Immunohistochemical staining confirmed their expression and subcellular localization. The interaction between CHKA and EGFR was examined using mass spectrometry, coimmunoprecipitation, polymerase chain reaction, and Western blotting. The effects of the CHKA/EGFR axis on the mitogen-activated protein kinase (MAPK) pathway were explored using polymerase chain reaction and Western blotting. Cell Counting Kit-8 (CCK-8), transwell, and wound-healing assays were conducted in glioma cell lines following CHKA knockdown and EGFR rescue. Finally, a nude mouse xenograft model was established to validate in vivo tumorigenicity and MAPK pathway activation. Results: CHKA was highly coexpressed with EGFR in specific glioma subpopulations, and their expression levels were positively correlated. Both genes were associated with advanced tumor grade and poor prognosis. CHKA interacted with EGFR and promoted its expression and phosphorylation. Silencing CHKA reduced EGFR levels and suppressed MAPK signaling. Functionally, CHKA enhanced glioma cell proliferation, migration, and invasion through EGFR upregulation. Moreover, CHKA knockdown inhibited tumor growth and MAPK activation in vivo , while EGFR overexpression restored tumorigenesis. Conclusions: CHKA drives glioma malignancy by regulating EGFR and activating the MAPK pathway. The CHKA/EGFR/MAPK axis represents a potential therapeutic target for glioma treatment.