Journal article

Perturbed BMP signaling and denervation promote muscle wasting in cancer cachexia.

Roberta Sartori, Adam Hagg, Sandra Zampieri, Andrea Armani, Catherine E Winbanks, Laís R Viana, Mouna Haidar, Kevin I Watt, Hongwei Qian, Camilla Pezzini, Pardis Zanganeh, Bradley J Turner, Anna Larsson, Gianpietro Zanchettin, Elisa S Pierobon, Lucia Moletta, Michele Valmasoni, Alberto Ponzoni, Shady Attar, Gianfranco Da Dalt Show all

Science Translational Medicine | American Association for the Advancement of Science | Published : 2021

Abstract

Most patients with advanced solid cancers exhibit features of cachexia, a debilitating syndrome characterized by progressive loss of skeletal muscle mass and strength. Because the underlying mechanisms of this multifactorial syndrome are incompletely defined, effective therapeutics have yet to be developed. Here, we show that diminished bone morphogenetic protein (BMP) signaling is observed early in the onset of skeletal muscle wasting associated with cancer cachexia in mouse models and in patients with cancer. Cancer-mediated factors including Activin A and IL-6 trigger the expression of the BMP inhibitor Noggin in muscle, which blocks the actions of BMPs on muscle fibers and motor nerves, ..

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Grants

Awarded by Alimentary Health


Awarded by Swedish Foundation for International Cooperation in Research and Higher Education


Awarded by Advanced Science Institute


Awarded by National Health and Medical Research Council


Awarded by European Research Council


Awarded by Institute of Genetics


Awarded by Studies


Awarded by Fondazione AIRC per la Ricerca sul Cancro


Awarded by H2020-MSCA-RISE


Awarded by National Multiple Sclerosis Society Michigan Chapter, Inc.


Awarded by Advanced Foods and Materials Canada


Funding Acknowledgements

Studies were supported by a project grant (1121500 awarded to P.G. and L.L.) from the National Health and Medical Research Council of Australia (NHMRC), an international collaboration project from the Swedish Foundation for International Co-operation in Research and Higher Education (STINT) awarded to L.L. and P.G., an Endeavour Research Fellowship from the Department of Education and Training, Australian Government to R.S., two postdoctoral fellowships from Fondazione Umberto Veronesi (ID2496 and ID3519 to R.S.) and a postdoctoral fellowship from the Association Francaise Contre les Myopathies (AFM-Telethon, ID21938 awarded to R.S.), funding awarded by the Italian Association for Cancer Research (AIRC IG -ID17388 and ID23257), ASI (MARS-PRE, project no DC-VUM-2017-006), and H2020-MSCA-RISE-2014 project no. 645648 "Muscle Stress Relief" awarded to M.S., funding awarded by the Italian Association for Cancer Research (AIRC IG 2018-ID.21963 project awarded to F.P.), project funding from the Stafford Fox Medical Research Foundation to awarded B.J.T., an Australian Post Graduate Award (Department of Education and Training, Australian Government), a PhD stipend top-up award from the Baker Heart and Diabetes Institute Bright Sparks program awarded to A.H., and a Senior Research Fellowship (1117835, NHMRC, Australia) awarded to P.G. The Baker Heart and Diabetes Institute is supported, in part, by an operational infrastructure support program from the Victorian Government.