期刊论文详细信息
Advanced Science
Homeostasis Imbalance of YY2 and YY1 Promotes Tumor Growth by Manipulating Ferroptosis
Hezhao Zhao1  Yanjun Li2  Zhuolin Li2  Mankun Wei2  Shourong Wu2  Vivi Kasim2  Juan Li2  Makoto Miyagishi3 
[1] Department of Gastrointestinal Surgery Chongqing University Cancer Hospital Chongqing University Chongqing 400030 China;Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University Chongqing 400044 China;Molecular Composite Physiology Research Group Health and Medical Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba 305‐8566 Japan;
关键词: ferroptosis;    lipid peroxidation;    p53‐independent;    Yin Yang 1;    Yin Yang 2;   
DOI  :  10.1002/advs.202104836
来源: DOAJ
【 摘 要 】

Abstract Ferroptosis is a type of programmed cell death caused by disruption of redox homeostasis and is closely linked to amino acid metabolism. Yin Yang 2 (YY2) and its homolog Yin Yang 1 (YY1) are highly homologous, especially in their zinc‐finger domains. Furthermore, they share a consensus DNA binding motif. Increasing evidences have demonstrated the tumor suppressive effect of YY2, in contrast with the oncogenic YY1; however, little is known about the biological and pathological functions of YY2. Here, it is determined that YY2 induces tumor cell ferroptosis and subsequently suppresses tumorigenesis by inhibiting solute carrier family 7 member 11 (SLC7A11) transcription, leading to the decreased glutathione biosynthesis. Furthermore, YY2 and YY1 bind competitively to the same DNA binding site in the SLC7A11 promoter and antagonistically regulate tumor cell ferroptosis, thus suggesting the molecular mechanism underlying their opposite regulation on tumorigenesis. Moreover, mutations of YY2 zinc‐finger domains in clinical cancer patients abrogate YY2/SLC7A11 axis and tumor cell ferroptosis. Together, these results provide a new insight regarding the regulatory mechanism of ferroptosis, and a mechanistic explanation regarding the tumor suppressive effect of YY2. Finally, these findings demonstrate that homeostasis between YY1 and YY2 is crucial for maintaining redox homeostasis in tumor cells.

【 授权许可】

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