BRAF(V600E) and microenvironment in thyroid cancer: a functional link to drive cancer progression.
BRAF(V600E) and microenvironment in thyroid cancer: a functional link to drive cancer progression.
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DOI：
10.1158/0008-5472.can-10-3844
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发表时间：
2011-04-01
期刊：
影响因子：
11.2
通讯作者：
Parangi S
中科院分区：
文献类型：
--
作者：
Nucera C;Lawler J;Parangi S
在美国和欧洲，甲状腺乳头状癌 (PTC) 的发病率持续上升，虽然大多数患者状况良好，但有些患者会复发并死于疾病。携带 BRAFV600E 突变的 PTC 患者似乎表现出更具侵袭性的临床行为，但人们对这种突变在肿瘤微环境关键过程（如肿瘤粘附、迁移、侵袭和转移）中的作用知之甚少。细胞外基质（ECM）微环境不仅是上皮和基质微环境的细胞成分的结构支架，而且还对细胞行为产生深远的影响，影响活力、增殖、粘附、运动。 BRAFV600E 对细胞表面受体（即整联蛋白）和 ECM 非细胞成分（即 TSP-1、FN）的影响似乎以细胞环境依赖性方式触发不同的病理生物学效应。本综述将重点关注 BRAFV600E 在调节 PTC 微环境的一些 ECM 非细胞成分和跨膜受体中的作用的最新进展，以便设计针对 BRAFV600E 多方面信号级联的新型靶向疗法。其中一些靶向治疗药物，例如 ATP 竞争性 BRAFV600E 抑制剂（即口服生物可利用的 PLX4720 和 PLX4032 化合物）已经在研究中。
Papillary thyroid cancer (PTC) rates continue to increase in the United States and Europe, and while most patients do well, some recur and die of their disease. Patients with PTC harboring the BRAFV600E mutation appear to display a more aggressive clinical behavior but little is known about the role of this mutation in crucial processes in the tumor microenvironment such as tumor adhesion, migration, invasion, and metastasis. The extracellular matrix (ECM) microenvironment is not merely a structural scaffold for the cellular elements of the epithelial and stromal microenvironment, but it elicits also a profound influence on cell behavior affecting viability, proliferation, adhesion, motility. The effects of BRAFV600E on cell surface receptors (i.e. integrins) and ECM non-cellular components (i.e. TSP-1, FN) appear to trigger different pathological biological effects in a cell context-dependent manner. This review will focus on the recent progress in understanding the role of BRAFV600E in the regulation of some ECM non-cellular components and trans-membrane receptors of the microenvironment in PTC in order to design novel targeted therapies directed at the BRAFV600E multifaceted signaling cascades. Some of these targeted therapeutics such as ATP-competitive BRAFV600E inhibitors (i.e. orally bioavailable PLX4720 and PLX4032 compounds) are already under investigation.