针对 ARID1A 缺陷型癌症中谷胱甘肽代谢的脆弱性。,Cancer Cell

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针对 ARID1A 缺陷型癌症中谷胱甘肽代谢的脆弱性。
Cancer Cell ( IF 48.8 ) Pub Date : 2019-01-24 , DOI: 10.1016/j.ccell.2018.12.009
Hideaki Ogiwara ₁ , Kazuaki Takahashi ₂ , Mariko Sasaki ₃ , Takafumi Kuroda ₂ , Hiroshi Yoshida ₄ , Reiko Watanabe ₄ , Ami Maruyama ₅ , Hideki Makinoshima ₆ , Fumiko Chiwaki ₇ , Hiroki Sasaki ₇ , Tomoyasu Kato ₈ , Aikou Okamoto ₉ , Takashi Kohno ₃

Affiliation

Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Molecular Oncology, The Jikei University Graduate School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Yamagata 997-0052, Japan; Shonai Regional Industry Promotion Center, Tsuruoka, Yamagata 997-0015, Japan.
Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Yamagata 997-0052, Japan.
Department of Translational Oncology, Fundamental Innovative Oncology Core Center, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Department of Gynecology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.

ARID1A 编码 SWI/SNF 染色质重塑因子，并且经常在各种癌症中发生突变。这项研究表明，ARID1A 缺陷的癌细胞特别容易受到抗氧化剂谷胱甘肽 (GSH) 和谷氨酸-半胱氨酸连接酶合成酶催化亚基 (GCLC)（一种 GSH 合成的限速酶）的抑制。GCLC 的抑制显着降低了 ARID1A 缺陷癌细胞中的 GSH，导致由过量活性氧引发的细胞凋亡。由于 SLC7A11 的表达受损，ARID1A 缺陷的癌细胞的脆弱性是由于 GSH 的基础水平低造成的。SLC7A11 编码的胱氨酸转运蛋白为细胞提供半胱氨酸，这是 GSH 的关键来源，其表达通过 ARID1A 介导的染色质重塑增强。因此，

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更新日期：2019-01-25

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