Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/98861
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dc.contributor.authorLokireddy, Sudarsanareddyen
dc.contributor.authorWijesoma, Isuru Wijerupageen
dc.contributor.authorBonala, Sabeeraen
dc.contributor.authorWei, Mengen
dc.contributor.authorSze, Siu Kwanen
dc.contributor.authorMcFarlane, Craigen
dc.contributor.authorKambadur, Ravien
dc.contributor.authorSharma, Mridulaen
dc.date.accessioned2013-07-31T09:17:24Zen
dc.date.accessioned2019-12-06T20:00:34Z-
dc.date.available2013-07-31T09:17:24Zen
dc.date.available2019-12-06T20:00:34Z-
dc.date.copyright2012en
dc.date.issued2012en
dc.identifier.citationLokireddy, S., Wijesoma, I., Bonala, S., Wei, M., Sze, S., McFarlane, C., Kambadur, R.,& Sharma, M. (2012). Myostatin is a novel tumoral factor that induces cancer cachexia. Biochemical Journal, 446(1), 23-36. [Retracted]en
dc.identifier.urihttps://hdl.handle.net/10356/98861-
dc.description.abstractHumoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGFβ (transforming growth factor β) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of musclespecific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin–proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type II B)/Smad and NF-κB (nuclear factor κB) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy–lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletalmuscles collected from C26 tumour-bearing mice.en
dc.language.isoenen
dc.relation.ispartofseriesBiochemical journalen
dc.subjectDRNTU::Science::Biological sciencesen
dc.title[Retracted] Myostatin is a novel tumoral factor that induces cancer cachexiaen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doi10.1042/BJ20112024en
item.fulltextNo Fulltext-
item.grantfulltextnone-
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