title: Interleukin-6--a key regulator of colorectal cancer development.
abstract: Growing evidence proposes an important role for pro-inflammatory cytokines during tumor development. Several experimental and clinical studies have linked the pleiotropic cytokine interleukin-6 (IL-6) to the pathogenesis of sporadic and inflammation-associated colorectal cancer (CRC). Increased IL-6 expression has been related to advanced stage of disease and decreased survival in CRC patients. According to experimental studies, these effects are mediated through IL-6 trans-signaling promoting tumor cell proliferation and inhibiting apoptosis through gp130 activation on tumor cells with subsequent signaling through Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3). During recent years, several therapeutics targeting the IL-6/STAT3 pathway have been developed and pose a promising strategy for the treatment of CRC. This review discusses the molecular mechanisms and possible therapeutic targets involved in IL-6 signaling in CRC.
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Maximilian J
authors.initials: MJ
authors.lastname: Waldner
authors.forename: Sebastian
authors.initials: S
authors.lastname: Foersch
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050822:Cytokine Receptor gp130 / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000970:Antineoplastic Agents; D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C494086:STAT3 protein, human
keywords: IL-6; colorectal cancer; interleukin-6