Deregulation in STAT signaling is important for cutaneous T-cell lymphoma (CTCL) pathogenesis and cancer progression

E Netchiporouk, IV Litvinov, L Moreau, M Gilbert… - Cell cycle, 2014 - Taylor & Francis
E Netchiporouk, IV Litvinov, L Moreau, M Gilbert, D Sasseville, M Duvic
Cell cycle, 2014Taylor & Francis
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 …
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.
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