title: Dual function of MyD88 in inflammation and oncogenesis: implications for therapeutic intervention.
abstract: OBJECTIVE
  Inflammation is emerging as a new hallmark of cancer, and the toll-like receptor and interleukin-1 receptor adaptor molecule MyD88 has been linked to tumorigenesis. The purpose of this review is to give a brief overview of the latest advances in understanding the complexity of MyD88 implication in tumorigenesis.
  
  
  RESULTS
  MyD88 is shown to play a protumorigenic role through two mechanisms. First, it activates the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in the hematopoietic compartment and in tumor cells, inducing an inflammatory environment favorable to carcinogenesis. Second, it plays a cell-autonomous role in Ras signaling and transformation, independently of its role in inflammatory signaling. MyD88 mediates the optimal activation of the Ras/extracellular signal-regulated kinase (ERK) pathway by binding to ERK and protecting it from dephosphorylation. This optimal activation of the Ras pathway is essential for the expression of important DNA repair enzymes, allowing cancer cells to efficiently repair damaged DNA. MyD88 is also shown in certain cases to play an antitumoral role through modulation of the immune response
  
  
  CONCLUSIONS
  These findings present a new dual function model for MyD88 implication in carcinogenesis making it a potential therapeutic target in cancer.
authors.affiliation: Lyon Cancer Research Center, University Claude Bernard Lyon1, INSERM U1052 - CNRS UMR5286, Centre Leon Berard, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Kfoury
authors.forename: François
authors.initials: F
authors.lastname: Virard
authors.forename: Toufic
authors.initials: T
authors.lastname: Renno
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coste
mesh_terms: D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D011518:Proto-Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D011518:Proto-Oncogene Proteins