PT  - JOURNAL ARTICLE
AU  - Lilli Winter
AU  - Monika Kustermann
AU  - Büsra Ernhofer
AU  - Harald Höger
AU  - Reginald E Bittner
AU  - Wolfgang M Schmidt
TI  - Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
AID  - 10.26508/lsa.202201367
DP  - 2022 Nov 01
TA  - Life Science Alliance
PG  - e202201367
VI  - 5
IP  - 11
4099  - https://www.life-science-alliance.org/content/5/11/e202201367.short
4100  - https://www.life-science-alliance.org/content/5/11/e202201367.full
SO  - Life Sci. Alliance2022 Nov 01; 5
AB  - 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.