E2F7 transcriptionally upregulates SPC24 to mediate aerobic Glycolysis and facilitate stemness of breast cancer.

Metabolic reprogramming characterized by aerobic glycolysis is observed in various cancers, including breast cancer (BC), exerting essential influence on maintaining cancer stemness. The abnormal expression of SPC24 is linked to the occurrence and development of various cancers, but its role in BC remains unelucidated. Bioinformatics analysis was undertaken to determine the levels of SPC24 and E2F7 in BC, and the enriched signaling pathways of SPC24 with differential expression, which were validated through cell experiments. The transcriptional regulatory relationship between E2F7 and SPC24 was also assessed through bioinformatics analysis, with validation completed by dual luciferase assay and chromatin immunoprecipitation (ChIP). To evaluate BC stemness, we employed the western blot (WB) to detect the levels of CD44, CD133, Oct-4, and ALDH1A1, and conducted the cell sphere formation. Flow cytometry was used to detect the proportion of stem cells. To assess the level of glycolysis in BC cells, we detected the expression of key proteins LDHA, HK2, and GLUT1 through WB, and measured the extracellular acidification rate and oxygen consumption rate with kits. Cell experiments combining bioinformatics analysis demonstrated that both E2F7 and SPC24 were greatly upregulated in BC, with SPC24 primarily enriched in the glycolysis metabolic pathway. Further experiments manifested that SPC24 reinforced cell stemness through aerobic glycolysis reprogramming, and SPC24 was modulated by transcription factor E2F7. E2F7 transcriptionally activates the upregulation of SPC24 in BC, which boosts stemness through aerobic glycolysis reprogramming.