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
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, ..View full abstract
Related Projects (2)
USING GENE DELIVERY TECHNOLOGIES TO DEFINE NOVEL MECHANISMS OF SKELETAL MUSCLE ADAPTATION, AND DEVELOP MUSCLE-DIRECTED INTERVENTIONS FOR FRAILTY AND SERIOUS ILLNESS
The focus of my research is to investigate the cellular mechanisms underlying regulation of skeletal muscle size and function in health and ..
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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
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Awarded by Fondazione AIRC per la Ricerca sul Cancro
Awarded by H2020-MSCA-RISE
Awarded by National Multiple Sclerosis Society Michigan Chapter, Inc.
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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.