Caveolin-3, MURC and Trim72 predict myogenic differentiation in the human embryonal rhabdomyosarcoma RD cell line

Caveolin-3 (Cav-3), muscle-restricted coiled coil MURC (also referred to as Cavin-4) and the recently identified large tripartite motif Trim72 are proteins controlling a number of important processes in skeletal muscle, ranging from myogenesis and insulin signaling up to sarcolemma repair. In this study we investigated their expression in rhabdomyosarcoma (RMS), a soft tissue tumor showing morphological and biochemical traits of the skeletal muscle lineage. Immunohistochemical analysis showed a similar pattern of expression of the three proteins in different human RMS samples. Immunoblotting analysis carried out using different RMS cell lines showed an increased expression of these proteins during myogenic differentiation as compared to proliferating cells. In addition, confocal microscopy analysis revealed that Cav-3, MURC and Trim72 all co-localize at the plasmalemma of differentiated embryonal RD cells. Ectopic expression of a point mutated Cav-3P104L form in RD cells was sufficient to mislocalize both MURC and Trim72 into perinuclear Golgi-like compartments, leading to a cell phenotype characterized by increased ERK phosphorylation and severe impairment of myogenic differentiation. Overall, these data suggest that a concurrent expression of Cav-3, MURC and Trim72 configures as a specific signature predicting and regulating cell differentiation in RMS.