Myosin II co-chaperone general cell UNC-45 overexpression is associated with ovarian cancer, rapid proliferation, and motility
Myosin II co-chaperone general cell UNC-45 overexpression is associated with ovarian cancer, rapid proliferation, and motility
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DOI：
10.2353/ajpath.2007.070325
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发表时间：
2007-11-01
影响因子：
6
通讯作者：
Roden, Richard B. S.
中科院分区：
文献类型：
--
作者：
Bazzaro, Martina;Santillan, Antonio;Roden, Richard B. S.
肿瘤细胞的增殖和转移均依赖于肌球蛋白H。由于β-45是一个功能性肌球蛋白H马达的分子伴侣，我们检测了卵巢肿瘤中一般细胞（GC）β-45亚型的表达。与正常卵巢表面上皮和良性囊腺瘤相比，浆液性卵巢癌中GC-45表达水平升高。高分期浆液性癌中GC <$-45的表达高于低分期浆液性癌。同样地，卵巢细胞系中GC <$-45转录物和蛋白水平高于永生化卵巢表面上皮细胞。通过异位表达升高GC <$-45水平可提高卵巢癌细胞增殖的速率，而siRNA敲低GC <$-45可抑制增殖而不改变肌球蛋白H水平。GC Ⅶ-45和肌球蛋白H在融合间期细胞的胞质中弥散分布，但在胞质分裂过程中两者都聚集在卵裂沟处。GC α-45和肌球蛋白H也被运输到卵巢癌细胞的前缘，在划痕试验中被诱导移动。GCX 45的敲低降低了卵巢癌细胞的扩散能力，而GCX 45的过表达增强了卵巢癌细胞的扩散能力。综上所述，这些发现提示GC Ⅶ-45蛋白在卵巢癌增殖和转移中的表达升高。
Both tumor cell proliferation and metastasis are dependent on myosin H. Because UNC-45 is required to chaperone die assembly of a functional myosin H 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 H levels. GC UNC-45 and myosin H were diffuse within the cytoplasm of confluent interphase cells, but both accumulated together at the cleavage furrow during cytokinesis. GC UNC-45 and myosin H 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.