Golubovskaya Vita M, Gross Steven, Kaur Aparna S, Wilson Richard I, Xu Li-Hui, Yang Xi Hui, Cance William G
Department of Surgery, University of Florida, Gainesville, FL 32610-0286, USA.
Mol Cancer Res. 2003 Aug;1(10):755-64.
Focal adhesion kinase (FAK) and Src have been shown to be overexpressed in colon cancer. We have studied the role of these two kinases in resistance to apoptosis. Adenovirus-containing FAK-CD (Ad-FAK-CD), a dominant-negative, COOH-terminal portion of FAK, was used to inhibit FAK and cause apoptosis. Colon cancer cell lines were more resistant to Ad-FAK-CD-induced detachment and apoptosis than the breast cancer cell line, BT474. Colon cancer cell lines overexpressed highly active Src and FAK. Ad-FAK-CD-induced apoptosis was significantly increased by PP2, an inhibitor of Src family kinases. Activation of caspase-3, down-regulation of FAK, and Src and AKT activities were demonstrated in Ad-FAK-CD + PP2-treated colon cancer cells undergoing apoptosis. The results suggest that FAK and Src are both important survival factors, playing a role in protecting colon cancer cell lines from Ad-FAK-CD-induced apoptosis. Dual inhibition of these kinases may be important for therapies designed to enhance the apoptosis in colon cancers.
粘着斑激酶（FAK）和Src已被证明在结肠癌中过表达。我们研究了这两种激酶在抗凋亡中的作用。含FAK - CD的腺病毒（Ad - FAK - CD），即FAK的显性负性COOH末端部分，被用于抑制FAK并诱导凋亡。结肠癌细胞系比乳腺癌细胞系BT474对Ad - FAK - CD诱导的脱离和凋亡更具抗性。结肠癌细胞系过表达高活性的Src和FAK。Src家族激酶抑制剂PP2显著增加了Ad - FAK - CD诱导的凋亡。在接受凋亡处理的Ad - FAK - CD + PP2处理的结肠癌细胞中，证实了半胱天冬酶 - 3的激活、FAK的下调以及Src和AKT活性。结果表明，FAK和Src都是重要的生存因子，在保护结肠癌细胞系免受Ad - FAK - CD诱导的凋亡中发挥作用。对这些激酶的双重抑制可能对旨在增强结肠癌凋亡的治疗很重要。
