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

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

American journal of cancer research (2017-10-06)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-CHIP/STUB1 Antibody, Chemicon®, from goat
Sigma-Aldrich
Anti-Rabbit IgG (whole molecule)–Peroxidase antibody produced in goat, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-Goat IgG (whole molecule)–Peroxidase antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution