HFE promotes mitotic cell division through recruitment of cytokinetic abscission machinery in hepatocellular carcinoma

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

1 Scopus Citations
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Author(s)

  • Pingping Dong
  • Ziqing Cai
  • Bingfeng Li
  • Yueqin Zhu
  • Alice K. Y. Chan
  • And 7 others
  • Michael W. L. Chiang
  • Chun Hang Au
  • Wing Kin Sung
  • Tan To Cheung
  • Chung Mau Lo
  • Kwan Man
  • Nikki P. Lee

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)4185–4199
Journal / PublicationOncogene
Volume41
Issue number36
Online published26 Jul 2022
Publication statusPublished - 2 Sept 2022

Abstract

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.

Citation Format(s)

HFE promotes mitotic cell division through recruitment of cytokinetic abscission machinery in hepatocellular carcinoma. / Dong, Pingping; Cai, Ziqing; Li, Bingfeng et al.
In: Oncogene, Vol. 41, No. 36, 02.09.2022, p. 4185–4199.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review