Roles of activated Src and Stat3 signaling in melanoma tumor cell growth

Niu, Guilian; Bowman, Tammy; Huang, Mei; Shivers, Steven C.; Reintgen, Douglas S.; Daud, Adil; Chang, Alfred E.; Kraker, Alan J.; Jove, Richard; Yu, Hua

doi:10.1038/sj.onc.1205859

Cited by 377 publications

(306 citation statements)

References 34 publications

(82 reference statements)

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“…In our cell model, inhibition of the PI3K/AKT did not reduce either transcription or translation of Mcl-1, thus excluding its implication. A previous study has shown that in melanoma cells, Mcl-1 is regulated by the Src/Stat-3 signaling pathway, which also controls spontaneous apoptosis (66). Although our results indicate that the MAPK/ERK is involved in the regulation of Mcl-1, we do not exclude the implication of additional signaling pathways, such as Src/Stat-3.…”

Section: Discussioncontrasting

confidence: 49%

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Chetoui

Sylla

Gagnon-Houde

et al. 2008

Molecular Cancer Research

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Resistance of malignant melanoma cells to Fas-mediated apoptosis is among the mechanisms by which they escape immune surveillance. However, the mechanisms contributing to their resistance are not completely understood, and it is still unclear whether antiapoptotic Bcl-2 -related family proteins play a role in this resistance. In this study, we report that treatment of Fas-resistant melanoma cell lines with cycloheximide, a general inhibitor of de novo protein synthesis, sensitizes them to anti-Fas monoclonal antibody (mAb) -induced apoptosis. The cycloheximide-induced sensitization to Fas-induced apoptosis is associated with a rapid down-regulation of Mcl-1 protein levels, but not that of Bcl-2 or Bcl-xL. Targeting Mcl-1 in these melanoma cell lines with specific small interfering RNA was sufficient to sensitize them to both anti-Fas mAb-induced apoptosis and activation of caspase-9.

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Section: Discussioncontrasting

confidence: 49%

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Chetoui

Sylla

Gagnon-Houde

et al. 2008

Molecular Cancer Research

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“…As a matter of fact, STAT3-binding motifs are present in the promoter of Mcl-1 (Puthier et al, 1999). Other studies have reported decreased Mcl-1 expression and increased apoptosis after disruption of phospho-STAT3 signaling (Niu et al, 2002;Lee et al, 2004;Nam et al, 2005). However, we can exclude an involvement of the JAK/ STAT3 pathway in the regulation of Mcl-1 in the present study, as LNCaP-IL-6 þ cells have been previously shown to lack phosphorylated STAT3 (Steiner et al, 2003).…”

Section: Discussionmentioning

confidence: 56%

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1

et al. 2006

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“…Loss of the tumor growth could result from several events including apoptosis and angiogenesis. Inhibition of STAT3 signaling has been shown to decrease the expression of antiapoptotic genes Bcl-xl and Mcl-1 (Catlett-Falcone et al, 1999;Niu et al, 2002a). STAT3 may contribute to tumor angiogenesis by upregulating transcription of vascular endothelial growth factor (Niu et al, 2002b).…”

Section: Discussionmentioning

confidence: 99%

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells

et al. 2005

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Signal transducers and activators of transcription (STATs) are latent transcription factors that mediate cytokine-and growth factor-induced transcription. Constitutive activation of STAT3 has been shown in human cancers and transformed cell lines. We report that STAT3, but not STAT1 and STAT5, becomes phosphorylated in response to epidermal growth factor (EGF) and achieves maximal induction of collagenase-1 (MMP-1) transcription by interacting with c-JUN. Phosphorylation of STAT3 protein is biphasic: the first peak within 30 min and the second peak between 4 and 8 h. Association of STAT3 with c-JUN is detected and its constituting STAT3 is increasingly phosphorylated. The STAT and AP-1 elements are necessary for effective induction of MMP-1 promoter by EGF. Mutation of AP-1 element closely located at the STAT site abolishes the binding not only of c-JUN but also of STAT3 to MMP-1 promoter, resulting in the loss of the responsiveness to EGF. By blocking STAT3 activity with the dominant-negative form, we show the requirement of STAT3 for EGF induction of MMP-1 and MMP-10 (stromelysin-2). Furthermore, expression of the dominant-negative STAT3 is sufficient to inhibit the constitutive and EGF-inducible cell migration and invasion and the tumor formation in nude mice. These results demonstrate that STAT3 phosphorylation and its possible interaction with c-JUN are required for the strong responsiveness of MMP-1 to EGF, and STAT3 activation is crucial for exhibition of malignant characteristics in T24 bladder cancer cells.

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Roles of activated Src and Stat3 signaling in melanoma tumor cell growth

Cited by 377 publications

References 34 publications

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells

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