生物
胞质分裂
脱落
癌症研究
有丝分裂
细胞分裂
河马信号通路
细胞生物学
核分裂突变
癌症
下调和上调
细胞生长
细胞周期
细胞
信号转导
遗传学
基因
作者
Pingping Dong,Ziqing Cai,Bingfeng Li,Yueqin Zhu,A. H. C. Chan,Michael Chiang,Chun Hang Au,Wing-Kin Sung,Tan To Cheung,Chung Mau Lo,Kwan Man,Nikki P. Lee
出处
期刊:Oncogene
[Springer Nature]
日期:2022-07-26
卷期号:41 (36): 4185-4199
被引量:1
标识
DOI:10.1038/s41388-022-02419-2
摘要
HFE (Hemochromatosis) is a conventional iron level regulator and its loss of function due to gene mutations increases the risk of cancers including hepatocellular carcinoma (HCC). Likewise, studies focusing on HFE overexpression in cancers are all limited to linking up these events as a consequence of iron level deregulation. No study has explored any iron unrelated role of HFE in cancers. Here, we first reported HFE as an oncogene in HCC and its undescribed function on promoting abscission in cytokinesis during mitotic cell division, independent of its iron-regulating ability. Clinical analyses revealed HFE upregulation in tumors linking to large tumor size and poor prognosis. Functionally and mechanistically, HFE promoted cytokinetic abscission via facilitating ESCRT abscission machinery recruitment to the abscission site through signaling a novel HFE/ALK3/Smads/LIF/Hippo/YAP/YY1/KIF13A axis. Pharmacological blockage of HFE signaling axis impeded tumor phenotypes in vitro and in vivo. Our data on HFE-driven HCC unveiled a new mechanism utilized by cancer cells to propel rapid cell division. This study also laid the groundwork for tumor intolerable therapeutics development given the high cytokinetic dependency of cancer cells and their vulnerability to cytokinetic blockage.
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