JAK-STAT signaling activated by Abl oncogenes

Danial, Nika N.; Rothman, Paul B.

doi:10.1038/sj.onc.1203484

Cited by 125 publications

(91 citation statements)

References 80 publications

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“…OA Timofeeva et al suppress oncogenesis and metastatic growth (Bowman et al, 2000;Danial and Rothman, 2000;Huang et al, 2002), and STAT1 deficiency has been found in some tumors (Abril et al, 1998;Sun et al, 1998;Pansky et al, 2000). Although Stat1-deficient mice do not display a heightened incidence of spontaneous neoplasms, they are more sensitive to chemical induction of tumors (Kaplan et al, 1998;Levy and Gilliland, 2000).…”

Section: Stat1 Is a Prosurvival Factor In Wilms' Tumormentioning

confidence: 99%

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

et al. 2006

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Wilms' tumor (WT), one of the most common pediatric solid cancers, arises in the developing kidney as a result of genetic and epigenetic changes that lead to the abnormal proliferation and differentiation of the metanephric blastema. As activation of signal transducers and activators of transcription (STATs) plays an important role in the maintenance/growth and differentiation of the metanephric blastema, and constitutively activated STATs facilitate neoplastic behaviors of a variety of cancers, we hypothesized that dysregulation of STAT signaling may also contribute to WT pathogenesis. Accordingly, we evaluated STAT phosphorylation patterns in tumors and found that STAT1 was constitutively phosphorylated on serine 727 (S727) in 19 of 21 primary WT samples and two WT cell lines. An inactivating mutation of S727 to alanine reduced colony formation of WT cells in soft agar by more than 80% and induced apoptosis under conditions of growth stress. S727-phosphorylated STAT1 provided apoptotic resistance for WT cells via upregulation of expression of the heat-shock protein (HSP)27 and antiapoptotic protein myeloid cell leukemia (MCL)-1. The kinase responsible for STAT1 S727 phosphorylation in WT cells was identified based upon the use of selective inhibitors as protein kinase CK2, not p38, MAP-kinase kinase (MEK)1/2, phosphatidylinositol 3 0 -kinase, protein kinase C or Ca/calmodulindependent protein kinase II (CaMKII). The inhibition of CK2 blocked the anchorage-independent growth of WT cells and induced apoptosis under conditions of growth stress. Our findings suggest that serine-phosphorylated STAT1, as a downstream target of protein kinase CK2, plays a critical role in the pathogenesis of WT and possibly other neoplasms with similar STAT1 phosphorylation patterns.

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Section: Stat1 Is a Prosurvival Factor In Wilms' Tumormentioning

confidence: 99%

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

et al. 2006

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“…The Abl proteins include the retrovirally transduced product of Abl, v-Abl, and the product of chromosomal translocations found in human leukemias BCR-ABL and TEL-ABL. There is increasing evidence suggesting that the full transforming activity of Abl involves the activation of several signaling pathways including Ras, PI3K/AKT and JAK/STAT/Pim (Danial and Rothman, 2000;Kharas and Fruman, 2005;Chen et al, 2008;Tao et al, 2008). For example, previous results suggested that v-Abl-induced AKT activation is a critical signaling pathway in v-Abl-induced cytokine-independent cell growth (Oki et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Oncogenic E17K mutation in the pleckstrin homology domain of AKT1 promotes v-Abl-mediated pre-B-cell transformation and survival of Pim-deficient cells

et al. 2010

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“…STAT3 is known to have oncogenic properties. [167][168][169][170][171] v-Abl and BCR-ABL induce constitutive STAT activity. 167,168 STAT transcription factors can induce antiapoptotic gene expression including Bcl-X L .…”

Section: Overview Of Jak/stat Pathwaymentioning

confidence: 99%

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

et al. 2008

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Mutations and chromosomal translocations occur in leukemic cells that result in elevated expression or constitutive activation of various growth factor receptors and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are often activated by mutations in upstream genes. The Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways are regulated by upstream Ras that is frequently mutated in human cancer. Recently, it has been observed that the FLT-3 and Jak kinases and the phosphatase and tensin homologue deleted on chromosome 10 ( PTEN) phosphatase are also frequently mutated or their expression is altered in certain hematopoietic neoplasms. Many of the events elicited by the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways have direct effects on survival pathways. Aberrant regulation of the survival pathways can contribute to uncontrolled cell growth and lead to leukemia. In this review, we describe the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize recent data regarding the regulation and mutation status of these pathways and their involvement in leukemia

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JAK-STAT signaling activated by Abl oncogenes

Cited by 125 publications

References 80 publications

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

Oncogenic E17K mutation in the pleckstrin homology domain of AKT1 promotes v-Abl-mediated pre-B-cell transformation and survival of Pim-deficient cells

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

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