{Reference Type}: Journal Article
{Title}: A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution.
{Author}: Zhang Y;Dos Santos M;Huang H;Chen K;Iyengar P;Infante R;Polanco PM;Brekken RA;Cai C;Caijgas A;Cano Hernandez K;Xu L;Bassel-Duby R;Liu N;Olson EN;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 8
{Year}: 2024 Aug 27
暂无{DOI}: 10.1016/j.celrep.2024.114587
{Abstract}: 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.