FOXM1 boosts glycolysis by upregulating SQLE to inhibit anoikis in breast cancer cells.

Abstract

Background: Resisting anoikis is a prerequisite for cancer to spread and invade and a major cause of cancer-related deaths. Yet, the intricate mechanisms of how cancer cells evade anoikis remain largely unknown. There is a significant need to explore how these mechanisms play out in breast cancer (BC).

Methods: Bioinformatics analysis revealed the expression levels of SQLE and FOXM1 in BC tissue, along with their correlation. The enrichment pathways of SQLE were also explored. qPCR detected the expression of SQLE and FOXM1 in BC cells. CCK-8 assessed cell viability, while flow cytometry measured anoikis. Western blot was employed to examine the protein expression of key genes in glycolytic metabolism and apoptosis-related proteins. Extracellular acidification rate was quantified, and corresponding kits evaluated glucose consumption, lactate production, and adenosine triphosphate levels in cells. Dual-luciferase reporter assays and chromatin immunoprecipitation tests unveiled the binding relationship between FOXM1 and SQLE.

Results: SQLE was found to be highly expressed in BC and enriched in pathways associated with anoikis and glycolysis. SQLE curbed anoikis in BC via the aerobic glycolysis pathway. There was also a direct binding between FOXM1 and SQLE and a positive correlation between their expression. Recovery experiments substantiated that FOXM1 targeted SQLE to suppress anoikis in BC cells.

Conclusion: FOXM1 upregulates SQLE, which in turn mediates glycolysis to suppress anoikis in BC. The FOXM1/SQLE axis is a promising therapeutic target for BC treatment.