MET molecular mechanisms and therapies in lung cancer
MET molecular mechanisms and therapies in lung cancer
复制标题
DOI：
10.4161/cam.4.1.10973
复制
发表时间：
2010-01-01
影响因子：
3.2
通讯作者：
Salgia, Ravi
中科院分区：
文献类型：
--
作者：
Lawrence, Ryan E.;Salgia, Ravi
MET酪氨酸激酶信号通路在包括肺癌在内的许多癌症中上调。该通路通常促进有丝分裂、细胞运动和细胞存活；但在癌症中，它也能促进细胞增殖、侵袭、转移和血管生成。激活配体肝细胞生长因子（HGF）通常由成纤维细胞和平滑肌细胞分泌，但也可以由肿瘤细胞产生。MET在肺癌中的上调是由过表达和突变引起的。这些突变可能因种族而异。MET信号影响细胞骨架蛋白，如paxillin，它参与细胞粘附、生长和运动。阻断MET信号传导的治疗方法正在研究中，包括使用：小干扰RNA、格尔达霉素、竞争性HGF同源物、诱饵受体和直接MET抑制剂，如K252a、SU11274、PHA665752和PF2341066。希望阻断MET信号传导有一天能成为一些肺癌的有效治疗方法。
The MET tyrosine kinase signaling pathway is upregulated in many cancers, including lung cancer. The pathway normally promotes mitosis, cell motility and cell survival; but in cancer it can also promote cell proliferation, invasion, metastasis and angiogenesis. The activating ligand, hepatocyte growth factor (HGF) is normally secreted by fibroblasts and smooth muscle cells, but can also be produced by tumor cells. MET upregulation in lung cancer is caused by overexpression and mutation. These mutations can vary with ethnicity. MET signaling affects cytoskeletal proteins such as paxillin, which participates in cell adhesion, growth and motility. Therapeutic approaches that block MET signaling are being studied, and include the use of: small interference RNA, Geldanamycin, competitive HGF homologues, decoy receptors and direct MET inhibitors such as K252a, SU11274, PHA665752 and PF2341066. It is hoped that blocking MET signaling may one day become an effective treatment for some lung cancers.