Homeostasis Imbalance of YY2 and YY1 Promotes Tumor Growth by Manipulating Ferroptosis.
Homeostasis Imbalance of YY2 and YY1 Promotes Tumor Growth by Manipulating Ferroptosis.
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YY2 和 YY1 的稳态失衡通过操纵铁死亡促进肿瘤生长
DOI：
10.1002/advs.202104836
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发表时间：
2022-05
期刊：
影响因子：
15.1
通讯作者：
Kasim, Vivi
中科院分区：
文献类型：
--
作者：
Li, Yanjun;Li, Juan;Li, Zhuolin;Wei, Mankun;Zhao, Hezhao;Miyagishi, Makoto;Wu, Shourong;Kasim, Vivi
铁凋亡是一种由氧化还原稳态破坏引起的程序性细胞死亡，与氨基酸代谢密切相关。Yin Yang 2（YY 2）和Yin Yang 1（YY 1）是高度同源的，特别是在它们的锌指结构域。此外，它们共享一个共有的DNA结合基序。越来越多的证据表明，与致癌的YY 1相比，YY 2具有抑瘤作用;然而，对YY 2的生物学和病理学功能知之甚少。在此，确定YY 2诱导肿瘤细胞铁凋亡并随后通过抑制溶质载体家族7成员11（SLC 7A 11）转录来抑制肿瘤发生，导致谷胱甘肽生物合成减少。此外，YY 2和YY 1竞争性结合到SLC 7A 11启动子中的相同DNA结合位点，并拮抗性地调节肿瘤细胞的铁凋亡，从而表明它们对肿瘤发生的相反调节的分子机制。此外，临床癌症患者中YY 2锌指结构域的突变消除YY 2/SLC 7A 11轴和肿瘤细胞铁凋亡。总之，这些结果提供了一个新的见解，关于铁凋亡的调节机制，和YY 2的肿瘤抑制作用的机制解释。最后，这些发现表明YY 1和YY 2之间的稳态对于维持肿瘤细胞中的氧化还原稳态至关重要。阴阳2（Yin Yang 2，YY 2）与著名的癌基因阴阳1（Yin Yang 1，YY 1）高度同源，但其功能尚不清楚。YY 2与YY 1竞争结合SLC 7A 11启动子并拮抗性调节，导致对谷胱甘肽合成、铁凋亡和肿瘤进展的相反调节，表明YY 2/YY 1稳态对于维持肿瘤中的氧化还原稳态至关重要。
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. Yin Yang 2 (YY2) is highly homologous with Yin Yang 1 (YY1), a famous oncogene; however, little is known about its functions. YY2 competes with YY1 to bind to SLC7A11 promoter and regulates it antagonistically, resulting in the opposite regulation on glutathione synthesis, ferroptosis, and tumor progression, indicating that YY2/YY1 homeostasis is crucial for maintaining redox homeostasis in tumors.
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影响因子：
5.7
作者：
Kakizaki F;Sonoshita M;Miyoshi H;Itatani Y;Ito S;Kawada K;Sakai Y;Taketo MM
通讯作者：
Taketo MM
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
64.8
作者：
Jiang, Le;Kon, Ning;Li, Tongyuan;Wang, Shang-Jui;Su, Tao;Hibshoosh, Hanina;Baer, Richard;Gu, Wei
通讯作者：
Gu, Wei