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

TitleDisruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting
Authors
Issue Date2012
PublisherImpact Journals LLC.
Citation
Aging, 2012, v. 4 n. 2, p. 133-143 How to Cite?
AbstractCancer 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, these effects may limit sarcomeric contractile ability and also predispose skeletal muscle to structural instability; associated with muscle wasting and fatigue in cachexia.
Persistent Identifierhttp://hdl.handle.net/10722/209338
ISSN
2015 Impact Factor: 3.979
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorShum, AMYen_US
dc.contributor.authorMahendradatta, Ten_US
dc.contributor.authorTaylor, RJen_US
dc.contributor.authorPainter, ABen_US
dc.contributor.authorMoore, MMen_US
dc.contributor.authorTsoli, Men_US
dc.contributor.authorTan, TCen_US
dc.contributor.authorClarke, SJen_US
dc.contributor.authorRobertson, GRen_US
dc.contributor.authorPolly, Pen_US
dc.date.accessioned2015-04-17T05:07:48Z-
dc.date.available2015-04-17T05:07:48Z-
dc.date.issued2012en_US
dc.identifier.citationAging, 2012, v. 4 n. 2, p. 133-143en_US
dc.identifier.issn1945-4589en_US
dc.identifier.urihttp://hdl.handle.net/10722/209338-
dc.description.abstractCancer 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, these effects may limit sarcomeric contractile ability and also predispose skeletal muscle to structural instability; associated with muscle wasting and fatigue in cachexia.en_US
dc.languageengen_US
dc.publisherImpact Journals LLC.en_US
dc.relation.ispartofAgingen_US
dc.titleDisruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wastingen_US
dc.typeArticleen_US
dc.identifier.emailShum, AMY: angie_smy@hotmail.comen_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid22361433en_US
dc.identifier.pmcidPMC3314175en_US
dc.identifier.hkuros242595en_US
dc.identifier.volume4en_US
dc.identifier.issue2en_US
dc.identifier.spage133en_US
dc.identifier.epage143en_US
dc.publisher.placeUnited Statesen_US

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