title: Deregulation in STAT signaling is important for cutaneous T-cell lymphoma (CTCL) pathogenesis and cancer progression.
abstract: Deregulation of STAT signaling has been implicated in the pathogenesis for a variety of cancers, including CTCL. Constitutive activation of STAT5 and STAT3 was observed in early and late stages of CTCL, respectively. In early stages, IL-2, IL-7 and IL-15 signaling via JAK1 and JAK3 kinases is believed to be responsible for activating STAT5, while in advanced stages development of IL-21 autocrine signaling is thought to be important for STAT3 activation. Recent molecular evidence further suggests that upregulation of STAT5 in early disease stages results in increased expression of oncogenic miR-155 microRNA that subsequently targets STAT4 expression on mRNA level. STAT4 signaling is known to be critical for T helper (Th) 1 phenotype differentiation and its loss results in a switch from Th1 to Th2 phenotype in malignant T cells. During this switch the expression of STAT6 is often upregulated in CTCL. In advanced stages, activation of STAT3 and STAT5 may become completely cytokine-independent and be driven only via constitutively active JAK1 and JAK3 kinases. Further research into the molecular pathogenesis of JAK/STAT signaling in this cancer may enable us to develop effective therapies for our patients.
authors.affiliation: a Division of Dermatology ; McGill University Health Centre ; Montréal , QC Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Netchiporouk
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Litvinov
authors.forename: Linda
authors.initials: L
authors.lastname: Moreau
authors.forename: Martin
authors.initials: M
authors.lastname: Gilbert
authors.forename: Denis
authors.initials: D
authors.lastname: Sasseville
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
mesh_terms: D018450:Disease Progression; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D035683:MicroRNAs; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: Cutaneous T-Cell Lymphoma (CTCL); Mycosis Fungoides; STAT3; STAT4; STAT5; Sézary Syndrome; and STAT6