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.
Original language | English (US) |
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Pages (from-to) | 3331-3335 |
Number of pages | 5 |
Journal | Cell Cycle |
Volume | 13 |
Issue number | 21 |
DOIs | |
State | Published - Nov 1 2014 |
Keywords
- And STAT6
- Cutaneous T-cell lymphoma (CTCL)
- Mycosis fungoides
- STAT3
- STAT4
- STAT5
- Sézary syndrome
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology