IL-9 and its receptor: from signal transduction to tumorigenesis.
IL-9 is a multifunctional cytokine secreted by TH2 lymphocytes. Besides its role during immune responses, its growth factor and antiapoptotic activities on multiple transformed cells suggest a potential role in tumorigenesis. Indeed, IL-9 overexpression induces thymic lymphomas in mice, and IL-9 production is associated with Hodgkin disease and HTLV-I transformed T cells in humans. IL-9 activities are mediated by a specific receptor chain that forms a heterodimeric receptor with the common gamma chain also involved in IL-2,4,7,15 and 21 signaling. The IL-9 receptor and common gamma chains associate with JAK1 and JAK3, respectively and trigger the STAT-1, -3 and -5, IRS and RAS-MAPK pathways. Moreover, in vitro, dysregulated IL-9 response can lead to autonomous cell growth and malignant transformation of lymphoid cells associated with constitutive activation of the Jak/STAT pathway.
Knoops
Laurent
L
Ludwig Institute for Cancer Research and Experimental Medicine Unit, Université de Louvain, UCL 74 59, Avenue Hippodrome 74, B-1200 Brussels, Belgium.
Renauld
Jean-Christophe
JC
D000818:Animals; D002461:Cell Line, Transformed; D006689:Hodgkin Disease / Q000378:metabolism; D006801:Humans; D016906:Interleukin-9 / Q000502:physiology*; D016393:Lymphoma, B-Cell / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053651:Receptors, Interleukin-9; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
C508045:IL9R protein, human; D016906:Interleukin-9; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9