Met endosomal signalling: In the right place, at the right time
Met endosomal signalling: In the right place, at the right time
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DOI：
10.1016/j.biocel.2014.01.009
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发表时间：
2014-04-01
影响因子：
4
通讯作者：
Kermorgant, Stephanie
中科院分区：
文献类型：
--
作者：
Barrow-McGee, Rachel;Kermorgant, Stephanie
受体酪氨酸激酶（RTK）、Met和/或其配体HGF的信号转导失调与癌症形成和转移进展相关，其中Met/HGF通常过表达或突变。因此，Met已成为癌症治疗的主要靶标，其抑制作用目前正在临床上进行测试。最近已经变得明显的是，Met不是仅在质膜处发出信号，而是从内体隔室发出内化后信号。因此，Met内吞运输是完全激活信号如Gab 1、ERK 1/2、STAT 3和Rac 1所必需的，所有这些信号都与细胞存活、侵袭和转移有关。Met降解和再循环之间平衡的改变也可能影响Met信号传导。此外，激酶结构域中的致癌Met突变触发组成性Met内化/再循环，导致“内体信号传导”和随后的细胞转化。以Met为例，本文概述了调节贩运和内体信号传导的分子机制可用于设计未来癌症治疗的证据。(C)2014爱思唯尔有限公司版权所有。
Deregulated signalling of the Receptor Tyrosine Kinase (RTK), Met, and/or its ligand HGF have been associated with cancer formation and progression to metastasis, with Met/HGF often overexpressed or mutated. Thus, Met has become a major target for cancer therapy and its inhibition is currently being tested in the clinic. It has recently become evident that, instead of signalling at the plasma membrane only, Met signals post-internalisation from endosomal compartments. Thus, Met endocytic trafficking is required for the full activation of signals such as Gab1, ERK 1/2, STAT3 and Rac1, all implicated in cell survival, invasion and metastasis. Modifications in the balance between degradation and recycling of Met may also impinge on Met signalling. Moreover, oncogenic Met mutations in the kinase domain trigger constitutive Met internalisation/recycling, leading to "endosomal signalling" and consequent cell transformation. Using Met as an example, this review outlines the evidence that the molecular mechanisms regulating trafficking and endosomal signalling may be exploited to design future cancer therapies. (C) 2014 Elsevier Ltd. All rights reserved.