<br>STING 抑制线粒体 VDAC2 以独立于先天免疫控制 RCC 生长,Advanced Science

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STING 抑制线粒体 VDAC2 以独立于先天免疫控制 RCC 生长
Advanced Science ( IF 14.3 ) Pub Date : 2022-11-29 , DOI: 10.1002/advs.202203718
Zhichuan Zhu _{1,

2} , Xin Zhou _{1,

3} , Hongwei Du _{1,

3} , Erica W Cloer ₁ , Jiaming Zhang ₄ , Liu Mei ₂ , Ying Wang _{1,

2} , Xianming Tan _{1,

5} , Austin J Hepperla _{1,

6,

7} , Jeremy M Simon _{1,

6,

7,

8} , Jeanette Gowen Cook _{1,

2} , Michael B Major ₉ , Gianpietro Dotti _{1,

3} , Pengda Liu _{1,

2}

Affiliation

Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, 02115, USA.
Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Cell Biology and Physiology, Department of Otolaryngology, Washington University in St. Louis, St. Louis, MO, 63130, USA.

STING 是一种先天免疫传感器，用于对病毒/细菌感染进行免疫监视并维持免疫友好的微环境以防止肿瘤发生。然而，STING 是否以及如何发挥先天免疫独立功能仍然难以捉摸。在这里，作者报告说，STING 表达在肾细胞癌 (RCC) 患者中增加，并通过涉及线粒体 ROS 维持和钙稳态的非典型先天免疫信号控制肿瘤生长。线粒体电压依赖性阴离子通道 VDAC2 被确定为新的 STING 结合伴侣。 STING 耗竭会增强 VDAC2/GRP75 介导的 MERC（线粒体-ER 接触）形成，从而增加线粒体 ROS/钙水平，损害线粒体功能，并抑制 mTORC1/S6K 信号传导，导致 RCC 生长迟缓。 STING 与 VDAC2 的相互作用通过 STING-C88/C91 棕榈酰化发生，并且通过 2-BP 抑制 STING 棕榈酰转移酶 ZDHHC 单独或与索拉非尼联合显着阻碍 RCC 细胞生长。总之，这些研究揭示了 STING 在调节 RCC 线粒体功能和生长方面的先天免疫独立功能，为靶向 STING/VDAC2 相互作用治疗 RCC 提供了理论基础。

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更新日期：2022-11-29

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