Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia

Roberto Mota, Jessica E. Rodríguez, Andrea Bonetto, Thomas M. O'Connell, Scott A. Asher, Traci L. Parry, Pamela Lockyer, Christopher R. McCudden, Marion E. Couch, Monte S. Willis

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation. Up to 80% of cancer patients experience cachexia, with 20-30% of cancer-related deaths directly linked to cachexia. Despite efforts to identify early cachexia and cancer relapse, clinically useful markers are lacking. Recently, we identified the role of muscle-specific ubiquitin ligases Atrogin-1 (MAFbx, FBXO32) and Muscle Ring Finger-1 in the pathogenesis of cardiac atrophy and hypertrophy. We hypothesized that during cachexia, the Atrogin-1 and MuRF1 ubiquitin ligases are released from muscle and migrate to the circulation where they could be detected and serve as a cachexia biomarker. To test this, we induced cachexia in mice using the C26 adenocarcinoma cells or vehicle (control). Body weight, tumor volume, and food consumption were measured from inoculation until ~day 14 to document cachexia. Western blot analysis of serum identified the presence of Atrogin-1 and MuRF1 with unique post-translational modifications consistent with mono- and poly- ubiquitination of Atrogin-1 and MuRF1 found only in cachectic serum. These findings suggest that both increased Atrogin-1 and the presence of unique post-translational modifications may serve as a surrogate marker specific for cachexia.

Original languageEnglish (US)
Pages (from-to)1948-1958
Number of pages11
JournalAmerican Journal of Cancer Research
Volume7
Issue number9
StatePublished - Jan 1 2017
Externally publishedYes

Keywords

  • Atrogin-1
  • Biomarkers
  • Cancer cachexia
  • FBXO32
  • Muscle ring Finger-1
  • TRIM63

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Mota, R., Rodríguez, J. E., Bonetto, A., O'Connell, T. M., Asher, S. A., Parry, T. L., Lockyer, P., McCudden, C. R., Couch, M. E., & Willis, M. S. (2017). Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia. American Journal of Cancer Research, 7(9), 1948-1958.