Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas

Dejean, Emilie; Renalier, Marie-Hélène; Foisseau, Marianne; Agirre, Xabier; Joseph, Nicole; Paiva, Geisilène Russano de; Saati, Talal Al; Soulier, Jean; Desjobert, Cécile; Lamant, Laurence; Prósper, Felipe; Felsher, Dean W.; Cavaillé, Jérôme; Prats, Hervé; Delsol, Georges; Giuriato, Sylvie; Meggetto, Fabienne

doi:10.1038/leu.2011.168

Cited by 101 publications

(80 citation statements)

References 48 publications

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“…Our group and others previously described a link between ALK and angiogenesis in lymphoma (11) and neuroblastoma (12). In ALCL, oncogenic ALK was shown to control VEGF expression in vitro in murine cells and human ALCL (11,13).…”

Section: Introductionmentioning

confidence: 99%

ALK-Dependent Control of Hypoxia-Inducible Factors Mediates Tumor Growth and Metastasis

et al. 2014

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Rearrangements involving the anaplastic lymphoma kinase (ALK) gene are defining events in several tumors, including anaplastic large-cell lymphoma (ALCL) and non-small cell lung carcinoma (NSCLC). In such cancers, the oncogenic activity of ALK stimulates signaling pathways that induce cell transformation and promote tumor growth. In search for common pathways activated by oncogenic ALK across different tumors types, we found that hypoxia pathways were significantly enriched in ALK-rearranged ALCL and NSCLC, as compared with other types of T-cell lymphoma or EGFR-and K-RAS-mutated NSCLC, respectively. Consistently, in both ALCL and NSCLC, we found that under hypoxic conditions, ALK directly regulated the abundance of hypoxia-inducible factors (HIF), which are key players of the hypoxia response in normal tissues and cancers. In ALCL, the upregulation of HIF1a and HIF2a in hypoxic conditions required ALK activity and its downstream signaling proteins STAT3 and C/EBPb. In vivo, ALK regulated VEGFA production and tumor angiogenesis in ALCL and NSCLC, and the treatment with the anti-VEGFA antibody bevacizumab strongly impaired ALCL growth in mouse xenografts. Finally, HIF2a, but not HIF1a, was required for ALCL growth in vivo whereas the growth and metastasis potential of ALK-rearranged NSCLC required both HIF1a and HIF2a. In conclusion, we uncovered an ALK-specific regulation of the hypoxia response across different ALK þ tumor types and propose HIFs as a powerful specific therapeutic target in ALK-rearranged ALCL and NSCLC. Cancer Res; 74(21); 6094-106. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 99%

ALK-Dependent Control of Hypoxia-Inducible Factors Mediates Tumor Growth and Metastasis

et al. 2014

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“…mediating oncogenic NPM-ALK signaling (28)(29)(30)(31). We have previously reported that the repression of miR-29a is dependent on the activity of both NPM-ALK and STAT3, and we demonstrated for the first time in ALCL that repression of miR-29a is likely mediated by epigenetic silencing (29).…”

Section: Introductionmentioning

confidence: 64%

Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth

Hoareau-Aveilla¹,

Valentin²,

Daugrois³

et al. 2015

Journal of Clinical Investigation

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“…The MIR15A/16-1 cluster has also been linked with the pathogenesis of several lymphoma types including mantle cell lymphoma (Chen et al, 2008;Zhang et al, 2012) and anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) (Dejean et al, 2011). In the latter case, the presence of hallmark ALK expression was found to down-regulate MIR16 expression in concert with hypoxiainduced factor 1a (HIF1A), which, in turn, induced expression of VEGFA in ALK + ALCL cases.…”

Section: Mir15a/16-1 Clustermentioning

confidence: 95%

MicroRNAs and lymphomagenesis: a functional review

Lawrie

2012

Br J Haematol

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SummaryThe relatively recent discovery of microRNAs (miRNAs) has exposed an extra layer of gene expression regulation that affects many physiological and pathological processes of biology. Dysregulation of miRNAs is a ubiquitous feature of cancer in general, including lymphomas. The identity of these aberrantly-expressed miRNAs has been thoroughly investigated in all but a few types of lymphomas, however their functional role in lymphomagenesis much less so. This review focuses on those miRNAs that have an experimentally confirmed functional role in the pathogenesis of the most frequent forms of lymphoma. In particular, the MIR15A/16-1 cluster, MIR21, MIR155, MIR17HG (MIR17-92 cluster), MIR34A and MIR125B, which have in vivo animal model evidence for their involvement in lymphomagenesis, are highlighted.

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Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas

Cited by 101 publications

References 48 publications

ALK-Dependent Control of Hypoxia-Inducible Factors Mediates Tumor Growth and Metastasis

ALK-Dependent Control of Hypoxia-Inducible Factors Mediates Tumor Growth and Metastasis

Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth

MicroRNAs and lymphomagenesis: a functional review

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