Epidermal growth factor receptor and cancer: control of oncogenic signalling by endocytosis.
Epidermal growth factor receptor and cancer: control of oncogenic signalling by endocytosis.
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DOI：
10.1111/j.1582-4934.2008.00298.x
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发表时间：
2008-09
影响因子：
5.3
通讯作者：
Madshus IH
中科院分区：
文献类型：
--
作者：
Grandal MV;Madshus IH
表皮生长因子受体(EGFR)和受体酪氨酸激酶(RTK)的EGFR/ErbB受体家族中的其他成员是重要的增殖、血管生成、迁移、肿瘤发生和转移的调节因子。ErbB蛋白的过度表达、突变、缺失和自分泌配体的产生导致了ErbB蛋白的异常激活。由于其他ErbB蛋白经常在同一细胞中额外表达和激活，导致同源和/或异源二聚体的形成，EGFR的信号输出是复杂的。特别是，EGFR与ErbB2的关联阻止了其下调，强调了细胞背景对EGFR效应的重要性。ErbB蛋白的信号既可以通过配体的解离导致去磷酸化而终止，也可以通过受体的降解而钝化。虽然已经描述了蛋白酶体靶向ErbB蛋白，但在配体诱导的内吞作用下，溶酶体的降解似乎在EGFR下调中发挥了主要作用。临床前和临床数据表明，EGFR在癌症，特别是在癌症、一些脑瘤和非小细胞肺癌中发挥着核心作用。这些研究进一步证实了EGFR在癌症治疗中是一个重要的分子靶点。本文就配体诱导的EGFR活化和细胞内下调的机制作一综述。对EGFR生物学的更好理解应该有助于开发针对EGFR诱导信号的更具肿瘤选择性的治疗方法。
The epidermal growth factor receptor (EGFR) and other members of the EGFR/ErbB receptor family of receptor tyrosine kinases (RTKs) are important regulators of proliferation, angiogenesis, migration, tumorigenesis and metastasis. Overexpression, mutations, deletions and production of autocrine ligands contribute to aberrant activation of the ErbB proteins. The signalling output from EGFR is complicated given that other ErbB proteins are often additionally expressed and activated in the same cell, resulting in formation of homo-and/or heterodimers. In particular, association of EGFR with ErbB2 prevents its down-regulation, underscoring the importance of the cellular background for EGFR effects. Signalling from ErbB proteins can either be terminated by dissociation of ligand resulting in dephosphorylation, or blunted by degradation of the receptors. Although proteasomal targeting of ErbB proteins has been described, lysosomal degradation upon ligand-induced endocytosis seems to play the major role in EGFR down-regulation. Preclinical and clinical data have demonstrated that EGFR is a central player in cancer, especially in carcinomas, some brain tumours and in non-small cell lung cancer. Such studies have further validated EGFR as an important molecular target in cancer treatment. This review focuses on mechanisms involved in ligand-induced EGFR activation and endocytic down-regulation. A better understanding of EGFR biology should allow development of more tumour-selective therapeutic approaches targeting EGFR-induced signalling.
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影响因子：
8
作者：
Davies, G. C.;Ryan, P. E.;Lipkowitz, S.
通讯作者：
Lipkowitz, S.
影响因子：
6.7
作者：
GULLICK, WJ
通讯作者：
GULLICK, WJ
影响因子：
50.3
作者：
Isaacs, JS;Xu, WP;Neckers, L
通讯作者：
Neckers, L
影响因子：
7.8
作者：
CARPENTIER, JL;GORDEN, P;ORCI, L
通讯作者：
ORCI, L
影响因子：
7.8
作者：
FELDER, S;LAVIN, J;SCHLESSINGER, J
通讯作者：
SCHLESSINGER, J