A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution Journal Article
| Authors: | Zhang, Y.; Dos Santos, M.; Huang, H.; Chen, K.; Iyengar, P.; Infante, R.; Polanco, P. M.; Brekken, R. A.; Cai, C.; Caijgas, A.; Cano Hernandez, K.; Xu, L.; Bassel-Duby, R.; Liu, N.; Olson, E. N. |
| Article Title: | A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution |
| 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. © 2024 The Author(s) |
| Keywords: | immunohistochemistry; controlled study; protein expression; sequence analysis; histopathology; nonhuman; mouse; animal tissue; gene overexpression; gene expression; gene expression profiling; animal experiment; animal model; atrophy; histology; cell culture; chromatin immunoprecipitation; gene therapy; upregulation; cachexia; short hairpin rna; molecular model; myogenin; myod protein; muscle atrophy; wnt signaling; denervation; adeno associated virus; aav; article; rna sequencing; follistatin; myostatin; multiomics; cp: cancer; cp: metabolism; single nucleus atac-seq; single nucleus multiome; single nucleus rna-seq |
| Journal Title: | Cell Reports |
| Volume: | 43 |
| Issue: | 8 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2024-08-27 |
| Start Page: | 114587 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2024.114587 |
| PROVIDER: | scopus |
| PUBMED: | 39116208 |
| PMCID: | PMC11472345 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
