STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity
Abstract: STING is an innate immune sensor for immune surveillance of viral/bacterial infection and maintenance of an immune‐friendly microenvironment to prevent tumorigenesis. However, if and how STING exerts innate immunity‐independent function remains elusive. Here, the authors report that STING expression is increased in renal cell carcinoma (RCC) patients and governs tumor growth through non‐canonical innate immune signaling involving mitochondrial ROS maintenance and calcium homeostasis. Mitochondrial voltage‐dependent anion channel VDAC2 is identified as a new STING binding partner. STING depletion potentiates VDAC2/GRP75‐mediated MERC (mitochondria‐ER contact) formation to increase mitochondrial ROS/calcium levels, impairs mitochondria function, and suppresses mTORC1/S6K signaling leading to RCC growth retardation. STING interaction with VDAC2 occurs through STING‐C88/C91 palmitoylation and inhibiting STING palmitoyl‐transferases ZDHHCs by 2‐BP significantly impedes RCC cell growth alone or in combination with sorafenib. Together, these studies reveal an innate immunity‐independent function of STING in regulating mitochondrial function and growth in RCC, providing a rationale to target the STING/VDAC2 interaction in treating RCC.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity ; day:29 ; month:11 ; year:2022 ; extent:20
Advanced science ; (29.11.2022) (gesamt 20)
- Creator
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Zhu, Zhichuan
Zhou, Xin
Du, Hongwei
Cloer, Erica W.
Zhang, Jiaming
Mei, Liu
Wang, Ying
Tan, Xianming
Hepperla, Austin J.
Simon, Jeremy M.
Cook, Jeanette Gowen
Major, Michael B.
Dotti, Gianpietro
Liu, Pengda
- DOI
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10.1002/advs.202203718
- URN
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urn:nbn:de:101:1-2022113014015003352091
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:24 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Zhu, Zhichuan
- Zhou, Xin
- Du, Hongwei
- Cloer, Erica W.
- Zhang, Jiaming
- Mei, Liu
- Wang, Ying
- Tan, Xianming
- Hepperla, Austin J.
- Simon, Jeremy M.
- Cook, Jeanette Gowen
- Major, Michael B.
- Dotti, Gianpietro
- Liu, Pengda
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