CSDE1 Drives Glycolysis and the Progression of Prostate Cancer Through RAC1-Dependent RAS/MAPK Activation

Prostate cancer (PCa) remains a leading cause of cancer-related morbidity and mortality among men, necessitating the elucidation of molecular drivers behind its progression. In this study, we demonstrated that CSDE1 was upregulated in PCa tissues, and its expression was associated with poorer progression-free survival in patients with high Gleason scores. Functional analyses revealed that CSDE1 knockdown reduced PCa cell proliferation, migration, and invasion, while suppressing metabolic activity, as evidenced by reduced extracellular acidification rates (ECAR), oxygen consumption rates (OCR), and lactate production. At the mechanistic level, CSDE1 was found to be associated with RAC1 expression and RAC1-related signaling markers, accompanied by changes in MAPK pathway phosphorylation. Genetic modulation of RAC1 partially reversed the cellular and metabolic effects associated with altered CSDE1 expression, supporting a functional role for RAC1 in CSDE1-associated phenotypes. In addition, CSDE1 expression was accompanied by increased levels of the glycolytic regulators GLUT1 and LDHA, and pharmacological inhibition of MAPK signaling partially attenuated CSDE1-associated glycolytic changes. In vivo models validated the oncogenic role of the CSDE1-RAC1 axis in tumor growth. Together, these findings support CSDE1 as a key driver that enhances RAC1-mediated MAPK signaling and metabolic profiles in PCa, suggesting that CSDE1 may serve as a promising prognostic biomarker and therapeutic target.