TY - JOUR T1 - Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201367 VL - 5 IS - 11 SP - e202201367 AU - Lilli Winter AU - Monika Kustermann AU - Büsra Ernhofer AU - Harald Höger AU - Reginald E Bittner AU - Wolfgang M Schmidt Y1 - 2022/11/01 UR - https://www.life-science-alliance.org/content/5/11/e202201367.abstract N2 - Aberrant expression of dystrophin, utrophin, dysferlin, or calpain-3 was originally identified in muscular dystrophies (MDs). Increasing evidence now indicates that these proteins might act as tumor suppressors in myogenic and non-myogenic cancers. As DNA damage and somatic aneuploidy, hallmarks of cancer, are early pathological signs in MDs, we hypothesized that a common pathway might involve the centrosome. Here, we show that dystrophin, utrophin, dysferlin, and calpain-3 are functional constituents of the centrosome. In myoblasts, lack of any of these proteins caused excess centrosomes, centrosome misorientation, nuclear abnormalities, and impaired microtubule nucleation. In dystrophin double-mutants, these defects were significantly aggravated. Moreover, we demonstrate that also in non-myogenic cells, all four MD-related proteins localize to the centrosome, including the muscle-specific full-length dystrophin isoform. Therefore, MD-related proteins might share a convergent function at the centrosome in addition to their diverse, well-established muscle-specific functions. Thus, our findings support the notion that cancer-like centrosome-related defects underlie MDs and establish a novel concept linking MDs to cancer. ER -