Activation of ferritin light chain (FTL) by transcription factor salmonella pathogenicity island 1 modulates glycolysis to drive metastasis of ovarian cancer cells.

BACKGROUND

Ovarian cancer (OC) is the most lethal gynecological cancer often diagnosed at an advanced stage due to a lack of effective biomarkers. Ferritin light chain (FTL) is implicated in the development of various cancers, but its impact on OC remains unknown.

RESEARCH DESIGN AND

METHODS

Bioinformatics methods were utilized to analyze FTL. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were employed for expression detection, and cell counting kit- 8, and transwell assays were for cell biological functions assessment. Extracellular acidification rate, oxygen consumption rate, and glycolytic metabolite contents were measured. Dual-luciferase and chromatin immunoprecipitation assay validated binding relationship. Xenografted tumor models in nude mice verified the role of FTL in vivo.

RESULTS

Cell function experiments revealed that FTL facilitated proliferation, migration, and invasion of OC cells. Rescue experiments unveiled that 2-Deoxy-D-glucose attenuated stimulation on OC cell metastasis and glycolysis by FTL overexpression. Salmonella pathogenicity island 1 (SPI1) up-regulated FTL expression to promote glycolysis and metastasis. FTL knockdown inhibited tumor growth and suppressed glycolysis and cell metastasis in vivo, while SPI1 overexpression attenuated these effects.

CONCLUSIONS

This study demonstrated pro-metastatic mechanisms of transcription factor SPI1/FTL axis in OC and suggested it as a potential target for treating OC metastasis.