Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting.

Aging
Angie M Y ShumPatsie Polly

Abstract

Cancer cachexia is a highly debilitating paraneoplastic disease observed in more than 50% of patients with advanced cancers and directly contributes to 20% of cancer deaths. Loss of skeletal muscle is a defining characteristic of patients with cancer cachexia and is associated with poor survival. The present study reveals the involvement of a myogenic transcription factor Myocyte Enhancer Factor (MEF) 2C in cancer-induced skeletal muscle wasting. Increased skeletal muscle mRNA expression of Suppressor of Cytokine Signaling (Socs) 3 and the IL-6 receptor indicative of active IL-6 signaling was seen in skeletal muscle of mice bearing the Colon 26 (C26) carcinoma. Loss of skeletal muscle structural integrity and distorted mitochondria were also observed using electron microscopy. Gene and protein expression of MEF2C was significantly downregulated in skeletal muscle from C26-bearing mice. MEF2C gene targets myozenin and myoglobin as well as myokinase were also altered during cachexia, suggesting dysregulated oxygen transport capacity and ATP regeneration in addition to distorted structural integrity. In addition, reduced expression of calcineurin was observed which suggested a potential pathway of MEF2C dysregulation. Together, th...Continue Reading

References

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Citations

Jan 25, 2013·Journal of Cachexia, Sarcopenia and Muscle·Hirak Der-TorossianMarion E Couch
May 2, 2014·Frontiers in Physiology·Patsie Polly, Timothy C Tan
Oct 8, 2014·Nature Reviews. Cancer·Josep M ArgilésFrancisco J López-Soriano
Sep 24, 2015·Physiological Genomics·Angie M Y ShumPatsie Polly
Nov 13, 2015·Expert Opinion on Investigational Drugs·F PennaP Costelli
Oct 16, 2015·Journal of the National Cancer Institute·Yu-Chou TsengChing-Shih Chen
Jan 30, 2018·Oxidative Medicine and Cellular Longevity·Justin P HardeeJames A Carson
May 21, 2019·Oncotarget·Kiran MadugulaPooja Jain
Mar 28, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Raymond D DevineLoren E Wold
Mar 6, 2019·Frontiers in Physiology·Fabio PennaPaola Costelli
Jan 23, 2020·Journal of Cachexia, Sarcopenia and Muscle·Thomas KunzkeMichaela Aichler
Feb 6, 2016·PloS One·Linyuan ShenLi Zhu
Jan 23, 2016·Oxidative Medicine and Cellular Longevity·Min Hee ChoiReshma Taneja
Apr 5, 2019·Journal of Muscle Research and Cell Motility·Daria NeyroudRussell T Hepple
Mar 15, 2015·Current Opinion in Clinical Nutrition and Metabolic Care·Josep M ArgilésSilvia Busquets
Jul 3, 2013·International Journal of Oncology·A Aria TzikaJosep M Argiles
Oct 17, 2019·Cold Spring Harbor Perspectives in Medicine·Anup K Biswas, Swarnali Acharyya
Feb 9, 2021·Experimental Biology and Medicine·Chenyuan LiShengrong Sun
Feb 16, 2021·Frontiers in Physiology·Jonathan M Memme, David A Hood
Oct 15, 2020·Journal of Cachexia, Sarcopenia and Muscle·Adeline DollyStéphane Servais
Mar 31, 2021·Journal of Cachexia, Sarcopenia and Muscle·Agnès Martin, Damien Freyssenet
Apr 4, 2021·International Journal of Molecular Sciences·Steffen H RaunLykke Sylow
Jul 3, 2021·Biomedicines·Michele MannelliTania Fiaschi
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Jessica L HalleJames A Carson
Jul 24, 2021·JPEN. Journal of Parenteral and Enteral Nutrition·Juquan SongSteven E Wolf

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Methods Mentioned

BETA
electron microscopy
transgenic
electrophoresis
PCR

Software Mentioned

geNorm
GraphPad Prism
GraphPad
Spot

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