%0 Journal Article
%T A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution.
%A Zhang Y
%A Dos Santos M
%A Huang H
%A Chen K
%A Iyengar P
%A Infante R
%A Polanco PM
%A Brekken RA
%A Cai C
%A Caijgas A
%A Cano Hernandez K
%A Xu L
%A Bassel-Duby R
%A Liu N
%A Olson EN
%J Cell Rep
%V 43
%N 8
%D 2024 Aug 27
%M 39116208
暂无%R 10.1016/j.celrep.2024.114587
%X Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single-nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-dependent gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. Short hairpin RNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of muscle atrophy associated with cancer cachexia and highlight potential therapeutic targets for this disorder.