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  • Original Paper
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The tumor suppressor activity of SOCS-1

Abstract

SOCS-1 is an inducible SH2-containing inhibitor of Jak kinases and as such can potently suppress cytokine signaling. SOCS-1 deficient mice die within the first three weeks of life from a myeloproliferative disorder driven by excessive interferon signaling. We report here that SOCS-1 inhibits proliferation signals induced by a variety of oncogenes active within the hematopoietic system. Ectopic expression of SOCS-1 abolished proliferation mediated by a constitutively active form of the KIT receptor, TEL-JAK2, and v-ABL, and reduced metastasis from BCR-ABL transformed cells. SOCS-1, however, did not interfere with v-SRC or RASV12 mediated cellular transformation. A mutant form of SOCS-1 unable to bind through its SH2 domain to tyrosine phosphorylated proteins could still inhibit KIT, but not TEL-JAK2, indicating multiple mechanisms for SOCS-1-mediated tumor suppression. We show that the steady state levels of TEL-JAK2 and to a greater extent v-ABL are diminished in the presence of SOCS-1. Lastly, we show that SOCS-1 −/− fibroblasts are more sensitive than wild type fibroblasts to either spontaneous or oncogene-induced transformation. These data suggest that loss-of-function of SOCS-1 may collaborate with a variety of hematopoietic oncogenes to facilitate tumor progression.

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Acknowledgements

This work was supported by grants from the Terry Fox Program Project of the National Cancer Institute of Canada (NCIC), by the Canadian Institutes of Health Research (CIHR) and La Ligue Nationale contre le Cancer. R Rottapel is a CIHR Investigator and D Barber is an NCIC Research Scientist. PD Sepulveda was supported as a Research Fellow by the CIHR and the Ligue Nationale contre le Cancer. The authors thank C Cantin for his expertise in cell sorting and D Birnbaum for NIH3T3 Ras V12 cells.

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Correspondence to Robert Rottapel or Paulo de Sepulveda.

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Rottapel, R., Ilangumaran, S., Neale, C. et al. The tumor suppressor activity of SOCS-1. Oncogene 21, 4351–4362 (2002). https://doi.org/10.1038/sj.onc.1205537

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