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GP130/JAK/STAT3 signaling pathway induces multiple myeloma

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

 

Multiple myeloma (MM) is a cancer that forms in plasma cell predominantly within bone marrow (BM), leads to gammopathy, bone lesions and kidney problems. Many genetic events that related to MM generation have been revealed. In the study that published on The Journal of Clinical Investigation, Dechow et al. determined GP130/JAK/STAT3 signaling pathway is sufficient to induce MM generation in mice retroviral murine BM transduction-transplantation model.

 

It has been reported that IL-6/JAK/STAT signaling pathway plays a critical role in MM development. The expression of GP130 is activated by the binding of IL-6 molecule to IL-6 receptor (IL-6R). Then, the complex triggers JAK and STAT3 phosphorylation, followed by target gene activation.

Researchers established a murine retroviral transduction-transplantation model, that expresses constitutively active GP130 (L-GP130), induces rapid MM development. Those mice showed characteristics of human MM, that induced by L-GP130 expression. Furthermore, researchers found the combination of GP130 signaling and carcinogenic MYC expression is necessary and sufficient for directly inducing MM phenotype in cell. The results indicates GP130 signaling is critical for MM pathogenesis, and GP130/JAK/STAT3 axis may have promising therapeutic targets for MM.

 

Reference:
J Clin Invest. 2014 Nov 10;10.1172/JCI69094

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