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FUNDC2,a mitochondrial outer membrane protein,mediates triple-negative breast cancer progression via the AKT/GSK3β/GLI1 pathway

查看全文 作　　者：Liyang [1]Yin;Renxian [1]Cao;Zhuoqing [1]Liu;Gang [1]Luo;Yu [1]Li;Xiaolong [1]Zhou;Xiguang [1]Chen;Ying [1]Wu;Jun [2]He;Xuyu [1]Zu;Yingying [1]Shen 高影响力作者 机构地区：[1]The First Affiliated Hospital,Cancer Research Institute,Hengyang Medical School,University of South China,Hengyang 421001,China;[2]The Nanhua Affiliated Hospital,Department of Spine Surgery,Hengyang Medical School,University of South China,Hengyang 421001,China高影响力机构 出　　处：《Acta Biochimica et Biophysica Sinica》索引2023年第55卷第11期,共14页高影响力期刊 基　　金：supported by the grants from the National Natural Science Foundation of China (No.81972487);the Natural Science Foundation of Hunan Province (Nos.2022JJ70038,2021JJ20039,and 2020JJ4551);the Health Commission of Hunan Province (Nos.20201926 and 202104070680);the Education Department of Hunan Province (No.20C1592). 摘　　要：Triple-negative breast cancer(TNBC)lacks effective therapeutic targets and has a poor prognosis,easy recurrence and metastasis.It is urgent and important to explore TNBC treatment targets.Through mass spectrometry com-bined with qRT-PCR validation in luminal A cells and TNBC cells,high-content screening and clinical sample analysis,FUNDC2 was discovered as a novel target.The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear.In this study,we find that FUNDC2 expression in TNBC tissues is sig-nificantly higher than that in luminal subtype breast cancer tissues.FUNDC2 silencing in TNBC cells significantly reduces cell proliferation,migration and invasion.As demonstrated in vivo using subcutaneous tumor xenografts in mice,FUNDC2 suppression significantly inhibits tumor growth.The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3βand GLI1,a key factor of the Hedgehog signaling pathway.There-fore,FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC. 关 键 词：FUNDC2 GLI1 triple-negative breast cancer(TNBC) therapeutic target
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