Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1640-1649 |
| Number of pages | 10 |
| Journal | American Journal of Pathology |
| Volume | 171 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2007 |
Bibliographical note
Funding Information:Supported by the United States Department of Defense (grant OC010017 ), The Johns Hopkins Fund for Medical Discovery (to R.B., I.-M.S., and R.B.S.R), the Public Health Service (grant RO1 CA122581 to R.B.S.R ), and the HERA Foundation (to M.B. and A.S.).
