RT Journal Article
SR Electronic
T1 Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201367
DO 10.26508/lsa.202201367
VO 5
IS 11
A1 Winter, Lilli
A1 Kustermann, Monika
A1 Ernhofer, Büsra
A1 Höger, Harald
A1 Bittner, Reginald E
A1 Schmidt, Wolfgang M
YR 2022
UL http://www.life-science-alliance.org/content/5/11/e202201367.abstract
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.