{"doi":"10.1002/advs.202203718","title":"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.","journal":"Advanced Science","year":2022,"id":237154,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":63,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.943,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":522204,"name":"Xin Zhou","orcid":"0000-0001-9281-3612","position":1,"is_corresponding":false},{"id":239811,"name":"Hongwei Du","orcid":"0000-0002-7997-4507","position":2,"is_corresponding":false},{"id":18207,"name":"Erica W. Cloer","orcid":null,"position":3,"is_corresponding":false},{"id":535431,"name":"Jiaming Zhang","orcid":"0000-0001-8520-566X","position":4,"is_corresponding":false},{"id":858930,"name":"Mei Liu","orcid":"0000-0001-6057-3028","position":5,"is_corresponding":false},{"id":537564,"name":"Ying Wang","orcid":"0000-0002-9940-7606","position":6,"is_corresponding":false},{"id":225652,"name":"Xianming Tan","orcid":"0000-0002-5478-2269","position":7,"is_corresponding":false},{"id":13551,"name":"Austin J. Hepperla","orcid":"0000-0002-0107-2001","position":8,"is_corresponding":false},{"id":11659,"name":"Jeremy M. Simon","orcid":"0000-0003-3906-1663","position":9,"is_corresponding":false},{"id":266825,"name":"Jeanette Gowen Cook","orcid":"0000-0003-0849-7405","position":10,"is_corresponding":false},{"id":18212,"name":"Michael B. Major","orcid":"0000-0002-6753-8513","position":11,"is_corresponding":false},{"id":84668,"name":"Gianpietro Dotti","orcid":null,"position":12,"is_corresponding":false},{"id":484232,"name":"Pengda Liu","orcid":"0000-0003-2755-3601","position":13,"is_corresponding":false},{"id":484229,"name":"Zhichuan Zhu","orcid":"0000-0003-0327-9978","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T00:22:08.925400Z","pmid":"36445063","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}