title: Stimulator of interferon genes (STING): A "new chapter" in virus-associated cancer research. Lessons from wild-derived mouse models of innate immunity.
abstract: Thanks to the numerous studies that have been carried out recently in the field of cytosolic DNA sensing, STING (Stimulator of Interferon Genes) is now recognized as a key mediator of innate immune signaling. A substantial body of evidence derived from in vivo mouse models demonstrates that STING-regulated pathways underlie the pathogenesis of many diseases including infectious diseases and cancers. It has also become evident from these studies that STING is a promising therapeutic target for the treatment of cancer. However, mouse strains commonly used for modelling innate immune response against infections or tumors do not allow investigators to accurately reproduce certain specific characteristics of immune response observed in human cells. In this review, we will discuss recent data demonstrating that the use of wild-derived genetically distinct inbred mice as a model for investigation into the innate immunity signaling networks may provide valuable insight into the STING-regulated pathways specific for human cells. The maximum complexity of STING-mediated mechanisms can probably be seen in case of DNA virus-induced carcinogenesis in which STING may perform unexpected biological activities. Therefore, in another part of this review we will summarize emerging data on the role of STING in human DNA virus-related oncopathologies, with particular attention to HPV-associated cervical cancer, aiming to demonstrate that STING indeed "starts a new chapter" in research on this issue and that wild-derived mouse models of STING-mediated response to infections will probably be helpful in finding out molecular basis for clinical observations.
authors.affiliation: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, United States; Institute of High-Tech Biomedicine, Petrozavodsk State University, 33 Lenin str., Petrozavodsk 185910, Russian Federation. Electronic address: Alexander.Poltorak@tufts.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Poltorak
authors.affiliation: Institute of High-Tech Biomedicine, Petrozavodsk State University, 33 Lenin str., Petrozavodsk 185910, Russian Federation. Electronic address: olya.kurmyshkina@yandex.ru.
authors.forename: Olga
authors.initials: O
authors.lastname: Kurmyshkina
authors.affiliation: Institute of High-Tech Biomedicine, Petrozavodsk State University, 33 Lenin str., Petrozavodsk 185910, Russian Federation. Electronic address: VolkovaTO@yandex.ru.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Volkova
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D000099197:STING Protein
chemical_list: D008565:Membrane Proteins; C532857:STING1 protein, human; D000099197:STING Protein; C530855:Sting1 protein, mouse
keywords: Cancer; DMXAA; Mouse model; Oncovirus; STING