The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells.
The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells.
复制标题
DOI：
--
复制
发表时间：
1998-12
期刊：
影响因子：
--
通讯作者：
LiHui Xu;Xihui Yang;R. Craven;W. Cance
中科院分区：
文献类型：
--
作者：
LiHui Xu;Xihui Yang;R. Craven;W. Cance
Focal adhesion kinase (FAK) is a tyrosine kinase that is linked to signaling pathways between cells and their extracellular matrix. An alternate transcript of the COOH-terminal region of the FAK gene, called FAK-related nonkinase, has been shown to act as an inhibitor of FAK in chicken embryo fibroblasts. We have designed an analogous segment of human FAK, FAK COOH-terminal domain (FAK-CD), and transfected this construct into human tumor cells. Expression of FAK-CD inhibited cell growth in BT474 human breast cancer cells and C8161 human melanoma cells. To characterize the nature of growth inhibition, we developed an inducible system of FAK-CD expression and demonstrated that the induced FAK-CD protein localized to focal adhesions, causing cellular rounding, an irreversible loss of adhesion, and subsequent cell death. In addition, expression of FAK-CD reduced tyrosine phosphorylation of FAK, suggesting that FAK-CD may be a potent inhibitor of FAK in human tumor cells.
