Biological significance of focal adhesion kinase in ovarian cancer - Role in migration and invasion
Biological significance of focal adhesion kinase in ovarian cancer - Role in migration and invasion
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DOI：
10.1016/s0002-9440(10)63370-6
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发表时间：
2004-10-01
影响因子：
6
通讯作者：
Hendrix, MJC
中科院分区：
文献类型：
--
作者：
Sood, AK;Coffin, JE;Hendrix, MJC
粘着斑激酶（FAK）是一种非受体酪氨酸激酶，由整合素聚集激活。关于FAK在卵巢癌迁移和侵袭中的功能作用的数据有限。在目前的研究中，FAK的表达进行了评估卵巢细胞系（非转化和癌症），12良性卵巢样本，并在79个浸润性上皮性卵巢癌。所有三个卵巢癌细胞系过表达FAK相比，非转化细胞。将称为FAK-related nonkinase（FRNK）的显性阴性构建体引入两种卵巢癌细胞系（SKOV 3和222）。FRNK促进了这些细胞系中FAK的去磷酸化，而不改变总FAK水平。此外，FRNK使卵巢癌细胞的体外侵袭能力降低了56%至85%，并使其迁移能力降低了52%至68%。FRNK转染的细胞也显示差的细胞铺展。免疫组化分析显示，所有良性卵巢标本的表面上皮都有弱的FAK表达。相反，68%的浸润性卵巢癌过表达FAK。FAK过表达与高分期、高分级、淋巴结阳性和远处转移显著相关（P均<1 cm），是生存不良的独立预测因子。这些数据表明，FAK在大多数浸润性卵巢癌中过表达，并在卵巢癌迁移和侵袭中发挥重要作用。因此，FAK可能是卵巢癌治疗的一个重要靶点。
Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is activated by integrin clustering. There are limited data regarding the functional role of FAK in ovarian cancer migration and invasion. In the current study, FAK expression was evaluated in ovarian cell lines (nontransformed and cancer), 12 benign ovarian samples, and in 79 invasive epithelial ovarian cancers. All three ovarian cancer cell lines overexpressed FAK compared to the nontransformed cells. The dominant-negative construct called FAK-related nonkinase (FRNK) was introduced into two ovarian cancer cell lines (SKOV3 and 222). FRNK promoted FAK dephosphorylation without changing total FAK levels in these cell lines. Furthermore, FRNK decreased the in vitro invasive ability of ovarian cancer cells by 56 to 85% and decreased migration by 52 to 68%. FRNK-transfected cells also displayed poor cell spreading. Immunohistochemical analysis revealed that the surface epithelium from all benign ovarian samples had weak FAK expression. In contrast, 68% of invasive ovarian cancers overexpressed FAK. FAK overexpression was significantly associated with high tumor stage, high tumor grade, positive lymph nodes and presence of distant metastasis (all P values 1 cm were independent predictors of poor survival. These data indicate that FAK is overexpressed in most invasive ovarian cancers and plays a functionally significant role in ovarian cancer migration and invasion. Thus, FAK may be an important therapeutic target in ovarian carcinoma.