Feed

Metabolic reprogramming towards enhanced glycolysis contributes to cervical cancer progression and radioresistance, but its upstream regulatory mechanisms remain poorly understood. Here, we investigated the role and underlying mechanisms of kinesin family member C1 (KIFC1) in glycolytic reprogramming and radiosensitivity in cervical cancer. KIFC1 expression and clinical relevance were analysed using public datasets and cervical cancer tissue microarrays. In vitro and in vivo assays were performed to evaluate the effects of KIFC1 on tumour growth, glycolysis and radiosensitivity. Transcriptomic and molecular interaction analyses were performed to define the KIFC1-SRSF3-PKM regulatory axis. KIFC1 was upregulated in cervical cancer tissues and associated with poor clinical outcomes. KIFC1 depletion inhibited tumour growth, reduced glycolytic activity and enhanced radiosensitivity both in vitro and in vivo. Mechanistically, KIFC1 may facilitate the nuclear localization of the splicing factor SRSF3, thereby influencing PKM alternative splicing. Loss of KIFC1 resulted in cytoplasmic retention of SRSF3 and a switch from the pro-glycolytic PKM2 isoform to PKM1, leading to impaired glycolysis. This splicing-mediated metabolic reprogramming was a key determinant of radiosensitization and could be partially reversed by pharmacological activation of PKM2. These findings identify the KIFC1-SRSF3-PKM axis as a novel splicing-metabolic checkpoint governing radiosensitivity in cervical cancer and highlight KIFC1 as a promising therapeutic target for improving radiotherapy efficacy in cervical cancer.