Mitochondrial Protein UCP1 Inhibits The Malignant Behaviors Of Triple-negative Breast Cancer Through Activation Of Mitophagy And Pyroptosis

Triple negative breast cancer(TNBC) was a huge threat to women for its high morbidity and malignancy.Effective therapeutic option of TNBC was still deficiency.mitochondrial uncoupling protein 1(UCP1)showed therapeutic potential on several cancers for its metabolism regulate potential,whereas the mechanism and downstream pathway of UCP1 were not fully elucidated.We found that UCP1 was negative regulated to the progress of TNBC.Overexpression of UCP1 could inhibit the proliferation and metastasis potential of TNBC,meanwhile induce the mitochondrial dysfunction,then motivate the mitophagy process.The activation of mitophagy was verified the downstream of UCP1 on TNBCs metastasis.GSDME was also motivated in the TNBC cells with UCP1 overexpression,and was found to be a core of pyroptosis to regulate the proliferation potential on TNBC cells,instead of apoptosis process in vitro and in vivo.Arresting the process of mitophagy weaken the regulation effect of UCP1 on metastasis of TNBC,similar to the impairment of GSDME activation to the proliferation regulation of UCP1 on TNBC.Thus,our result suggested that UCP1 could inhibit the process of TNBC through the motivation of mitophagy and pyroptosis,and showed potential on novel therapeutic target of TNBC.