Choline kinase alpha regulates autophagy-associated exosome release to promote glioma cell progression.

Abstract

Glioma is the most common primary intracranial malignant tumor in adults, with a poor prognosis. Exosomes released by tumor cells play a crucial role in tumor development, metastasis, angiogenesis, and other biological processes. Despite this significance, the precise molecular mechanisms governing exosome secretion and their impact on tumor progression remain incompletely understood. While Choline Kinase Alpha (CHKA) has been implicated in promoting various types of tumors, its specific role in glioma pathogenesis remains unclear. Our study initially demonstrates that CHKA enhances the proliferation, migration, and invasion abilities of glioma cells. Interestingly, CHKA also stimulates the release of exosomes from glioma cells. Mechanistically, reduced CHKA expression hampers exosome secretion by elevating autophagy levels in gliomas, whereas counteracting the autophagy elevation resulting from CHKA downregulation restores the release of exosomes. Notably, exosomes derived from glioma cells with normal CHKA expression exhibit a greater capacity to promote glioma progression compared to those derived from cells with low CHKA expression. Overall, our findings suggest that CHKA modulates exosome secretion via an autophagy-dependent pathway, thereby facilitating the proliferation, migration, and invasion of glioma cells.