Cross talk between oxidative stress and hypoxia via thioredoxin and HIF-2α drives metastasis of hepatocellular carcinoma.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Man-Qing CaoTi Zhang

Abstract

Oxidative stress and hypoxia are two opposite microenvironments involved in HCC metastasis. Thioredoxin (TXN) and hypoxia-inducible factor 2α (HIF-2α) are typical proteins involved in these two different microenvironments, respectively. How these two factors interact to influence the fate on tumor cells remains unknown. Hypoxia facilitated HCC cells withstood oxidative stress and eventually promoted HCC cells metastasis, in which TXN and HIF-2α were mostly involved. Upregulation of TXN/HIF-2α correlated with poor HCC prognosis and promoted HCC metastasis both in vitro and in vivo. Epithelial-mesenchymal transition (EMT) process was involved in TXN/HIF-2α-enhanced invasiveness of HCC cells. Additionally, the stability and activity of HIF-2α were precisely regulated by TXN via SUMOylation and acetylation, which contributed to HCC metastasis. Our data revealed that the redox protein TXN and HIF-2α are both associated with HCC metastasis, and the fine regulation of TXN on HIF-2α contributes essentially during the process of metastasis. Our study provides new insight into the interaction mechanism between hypoxia and oxidative stress and implies potential therapeutic benefits by targeting both TXN and HIF-2α in the treatment of HCC ...Continue Reading

References

Sep 27, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dylan T JonesAdrian L Harris
May 30, 2009·Nature Reviews. Drug Discovery·Dunyaporn TrachoothamPeng Huang
Dec 23, 2009·Nucleic Acids Research·Martijn van HagenAlfred C O Vertegaal
Apr 29, 2010·Science Translational Medicine·Shannon L StottShyamala Maheswaran
Jun 3, 2010·Current Topics in Microbiology and Immunology·Alexander PietrasSven Påhlman
Jul 19, 2012·The Journal of Biological Chemistry·Rui ChenJoseph A Garcia
Aug 31, 2012·The New England Journal of Medicine·Zhengping ZhuangKarel Pacak
May 4, 2013·The Journal of Biological Chemistry·Qiulin TanFrank S Lee
Oct 19, 2013·Cancer Cell·Sakari Vanharanta, Joan Massagué
Aug 12, 2014·Nature Medicine·Min XuJoseph A Garcia
Sep 23, 2014·International Journal of Cancer. Journal International Du Cancer·Hongmei ZengXue Qin Yu
Aug 27, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Manqing CaoTi Zhang
Oct 16, 2015·Nature·Elena PiskounovaSean J Morrison
Oct 31, 2015·Journal of Neuro-oncology·David TaïebPhilippe Metellus
Nov 4, 2016·Nature·Wenfang ChenJames Brugarolas
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

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