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; Cosimo Sperti; Monika Kustermann; Rachel E Thomson; Lars Larsson; Kate L Loveland; Paola Costelli; Aram Megighian; Stefano Merigliano; Fabio Penna; Paul Gregorevic; Marco Sandri

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

DOI: 10.1126/scitranslmed.aay9592

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, ..

View full abstract

University of Melbourne Researchers

Adam Hagg Author Anatomy and Physiology

Rachel Thomson Author Anatomy and Physiology

Hongwei Qian Author Anatomy and Physiology

Kevin Watt Author Anatomy and Physiology

Paul Gregorevic Author Anatomy and Physiology

Related Projects (2)

INVESTIGATING FOLLISTATIN-BASED INTERVENTIONS FOR LONG TERM-PROTECTION AGAINST FRAILTY ASSOCIATED WITH CHRONIC ILLNESS AND AGING

Effective therapies are urgently needed to combat frailty arising from muscle wasting associated with chronic illness and aging. The propose..

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 ..

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.