Shibata K, Kikkawa F, Nawa A, Thant A A, Naruse K, Mizutani S, Hamaguchi M
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Cancer Res. 1998 Mar 1;58(5):900-3.
Cell adhesion to the extracellular matrix appears to trigger a cascade of intracellular signalings. We have shown previously that treatment of ovarian cancer cells with peritoneal conditioned medium or purified fibronectin (FN) activated matrix metalloproteinase 9 secretion and, thereby, cancer cell invasion. By use of antisense oligonucleotides to focal adhesion kinase (FAK) and a dominant-negative mutant of ras (S17Nras), we found that both FAK and c-Ras were required for the activation of matrix metalloproteinase 9 secretion by FN. In addition, both antisense oligonucleotides to FAK and S17Nras inhibited mitogen-activated protein kinase activation by FN treatment, suggesting the involvement of mitogen-activated protein kinase in the FN-dependent signaling.
细胞与细胞外基质的黏附似乎会引发一系列细胞内信号传导。我们之前已经表明，用腹膜条件培养基或纯化的纤连蛋白（FN）处理卵巢癌细胞会激活基质金属蛋白酶9的分泌，从而促进癌细胞侵袭。通过使用针对粘着斑激酶（FAK）的反义寡核苷酸和ras的显性负突变体（S17Nras），我们发现FAK和c-Ras都是FN激活基质金属蛋白酶9分泌所必需的。此外，针对FAK和S17Nras的反义寡核苷酸都抑制了FN处理引起的丝裂原活化蛋白激酶的激活，这表明丝裂原活化蛋白激酶参与了FN依赖性信号传导。
