癌症中的黏着斑激酶和 p53 信号转导通路。
Focal adhesion kinase and p53 signal transduction pathways in cancer.
机构信息
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
出版信息
Front Biosci (Landmark Ed). 2010 Jun 1;15(3):901-12. doi: 10.2741/3653.
Abstract
Human cancer is characterized by a process of tumor cell motility, invasion, and metastasis. One of the critical tyrosine kinases that is linked to these processes of tumor invasion and survival is the Focal Adhesion Kinase (FAK). Our laboratory was the first to isolate FAK from human tumors, and we had demonstrated that FAK mRNA was up-regulated in invasive and metastatic human breast and colon cancer samples. We have cloned FAK promoter and have found that FAK promoter contains p53 binding sites, and that p53 inhibits FAK transcription and regulates its expression in tumor samples. In addition, we have found a high correlation between FAK overexpression and p53 mutations in 600 population-based series of breast cancer patients. found that N-myc binds FAK promoter and induces FAK transcription in neuroblastoma cells. Thus, this review will be focused on FAK and p53 signal transduction pathways in cancer.
摘要
人类癌症的特征是肿瘤细胞的运动性、侵袭性和转移性。与肿瘤侵袭和存活相关的关键酪氨酸激酶之一是粘着斑激酶 (FAK)。我们的实验室是第一个从人类肿瘤中分离出 FAK 的实验室，我们已经证明 FAK mRNA 在侵袭性和转移性人乳腺癌和结肠癌样本中上调。我们已经克隆了 FAK 启动子，发现 FAK 启动子包含 p53 结合位点，p53 抑制 FAK 转录并调节其在肿瘤样本中的表达。此外，我们还发现 600 例基于人群的乳腺癌患者中 FAK 过表达与 p53 突变之间存在高度相关性。发现 N-myc 结合 FAK 启动子并在神经母细胞瘤细胞中诱导 FAK 转录。因此，本综述将集中讨论 FAK 和 p53 信号转导通路在癌症中的作用。
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A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth.一种靶向粘着斑激酶Y397位点的小分子抑制剂——1,2,4,5-苯四胺四盐酸盐可抑制肿瘤生长。
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