Myosin II co-chaperone general cell UNC-45 overexpression is associated with ovarian cancer, rapid proliferation, and motility.
Both tumor cell proliferation and metastasis are dependent on myosin II. Because UNC-45 is required to chaperone the assembly of a functional myosin II motor, we examined the expression of the general cell (GC) UNC-45 isoform in ovarian tumors. Serous carcinoma expressed elevated levels of GC UNC-45 compared with normal ovarian surface epithelium and benign cystadenoma. High-stage exhibited greater GC UNC-45 expression than low-stage serous carcinoma. Similarly, GC UNC-45 transcripts and protein levels were higher in ovarian cell lines than in immortalized ovarian surface epithelial cells. Elevation of GC UNC-45 levels by ectopic expression enhanced the rate of ovarian cancer cell proliferation, whereas siRNA knockdown of GC UNC-45 suppressed proliferation without altering myosin II levels. GC UNC-45 and myosin II were diffuse within the cytoplasm of confluent interphase cells, but both accumulated together at the cleavage furrow during cytokinesis. GC UNC-45 and myosin II also trafficked to the leading edges of ovarian cancer cells induced to move in a scratch assay. Knockdown of GC UNC-45 reduced the spreading ability of ovarian cancer cells whereas it was enhanced by GC UNC-45 overexpression. In sum, these findings implicate elevated GC UNC-45 protein expression in ovarian carcinoma proliferation and metastasis.
Bazzaro
Martina
M
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Santillan
Antonio
A
Lin
Zhenhua
Z
Tang
Taylor
T
Lee
Michael K
MK
Bristow
Robert E
RE
Shih
Ie-Ming
IeM
Roden
Richard B S
RB
D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology*; D024462:Myosin Type II / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000502:physiology; D011817:Rabbits
D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; C509158:UNC45A protein, human; D024462:Myosin Type II