{"doi":"10.17615/k8kn-qb10","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":"UNC Libraries","year":2024,"id":499889,"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":0,"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":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1349385,"name":"Major M.B","orcid":null,"position":1,"is_corresponding":false},{"id":1349386,"name":"Simon J.M","orcid":null,"position":2,"is_corresponding":false},{"id":1349387,"name":"Mei L","orcid":null,"position":3,"is_corresponding":false},{"id":1349388,"name":"Cloer E.W","orcid":null,"position":4,"is_corresponding":false},{"id":1349389,"name":"Cook J.G","orcid":null,"position":5,"is_corresponding":false},{"id":1349390,"name":"Hepperla A.J","orcid":null,"position":6,"is_corresponding":false},{"id":1348565,"name":"Liu P","orcid":null,"position":7,"is_corresponding":false},{"id":136611,"name":"J Zhang","orcid":null,"position":8,"is_corresponding":false},{"id":298781,"name":"Heng Du","orcid":"0000-0001-9067-0910","position":9,"is_corresponding":false},{"id":1349038,"name":"Tan X","orcid":"0000-0003-2185-2416","position":10,"is_corresponding":false},{"id":84668,"name":"Gianpietro Dotti","orcid":null,"position":11,"is_corresponding":false},{"id":290934,"name":"Xuedong Zhou","orcid":"0000-0002-9319-7302","position":12,"is_corresponding":false},{"id":1349391,"name":"Zhu Z","orcid":null,"position":13,"is_corresponding":false},{"id":1349384,"name":"Yu-Yan Wang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:10:04.829419Z","pmid":null,"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":[]}