Journal article

Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt-beta-catenin-mediated intestinal tumor growth and regeneration

Toby J Phesse, Michael Buchert, Emma Stuart, Dustin J Flanagan, Maree Faux, Shoukat Afshar-Sterle, Francesca Walker, Hui-Hua Zhang, Cameron J Nowell, Robert Jorissen, Chin Wee Tan, Yumiko Hirokawa, Moritz F Eissmann, Ashleigh R Poh, Jordane Malaterre, Helen B Pearson, David G Kirsch, Paolo Provero, Valeria Poli, Robert G Ramsay Show all

SCIENCE SIGNALING | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2014

Abstract

Most colon cancers arise from somatic mutations in the tumor suppressor gene APC (adenomatous polyposis coli), and these mutations cause constitutive activation of the Wnt-to-β-catenin pathway in the intestinal epithelium. Because Wnt-β-catenin signaling is required for homeostasis and regeneration of the adult intestinal epithelium, therapeutic targeting of this pathway is challenging. We found that genetic activation of the cytokine-stimulated pathway mediated by the receptor gp130, the associated Jak (Janus kinase) kinases, and the transcription factor Stat3 (signal transducer and activator of transcription 3) was required for intestinal regeneration in response to irradiation-induced dam..

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Grants

Awarded by Royal Melbourne Hospital


Awarded by Cancer Council of Victoria


Awarded by NHMRC


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

Funding: This work was supported by Ludwig Cancer Research, the Victorian State Government Operational Infrastructure Support, the Independent Research Institutes Infrastructure Support Scheme (IRIISS) scheme of the National Health and Medical Research Council Australia (NHMRC), a grant from the Royal Melbourne Hospital #605030 (E. V. and T.J.P.), a grant from the Cancer Council of Victoria #APP1020716 (E. V. and T.J.P.), and NHMRC grants #603127 (T.J.P. and M. B.), #566679 (E. V.), #487922 (M. E., R. G. R., and M. B.), #433617, #603122 (M. E.), and #1064987 (T.J.P., M. B., and M. E.). M. E. and R. G. R. are NHMRC Senior Research Fellows.