Emerging functions of the EGFR in cancer.
Emerging functions of the EGFR in cancer.
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DOI：
10.1002/1878-0261.12155
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发表时间：
2018-01
影响因子：
6.6
通讯作者：
Lanzetti L
中科院分区：
文献类型：
--
作者：
Sigismund S;Avanzato D;Lanzetti L
表皮生长因子受体（EGFR）的生理功能是调节上皮组织的发育和稳态。在病理学背景下，主要是在肺癌和乳腺癌以及胶质母细胞瘤中，EGFR是肿瘤发生的驱动因素。EGFR在癌症中的不适当活化主要由基因组位点的扩增和点突变引起，但也描述了由于自分泌/旁分泌机制导致的转录上调或配体过量产生。此外，EGFR越来越多地被认为是肿瘤耐药的生物标志物，因为已经发现其扩增或继发突变在药物压力下出现。除了该受体在正常上皮中发挥的突出功能之外，该证据还促使人们对EGFR在生理和病理水平上的作用进行深入研究。尽管在过去的二十年中获得了大量的知识，但EGFR的先前未被识别的（本文定义为“非规范”）功能目前正在出现。在这里，我们将首先回顾经典配体诱导的EGFR信号通路，特别强调其在人类肿瘤中通过内吞和颠覆的调节。然后，我们将集中在揭示非典型EGFR功能的最新进展，在压力诱导的贩运，自噬和能量代谢，对未来的治疗应用前景。
The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure. This evidence, in addition to the prominent function that this receptor plays in normal epithelia, has prompted intense investigations into the role of the EGFR both at physiological and at pathological level. Despite the large body of knowledge obtained over the last two decades, previously unrecognized (herein defined as ‘noncanonical’) functions of the EGFR are currently emerging. Here, we will initially review the canonical ligand‐induced EGFR signaling pathway, with particular emphasis to its regulation by endocytosis and subversion in human tumors. We will then focus on the most recent advances in uncovering noncanonical EGFR functions in stress‐induced trafficking, autophagy, and energy metabolism, with a perspective on future therapeutic applications.
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影响因子：
29
作者：
Babic I;Anderson ES;Tanaka K;Guo D;Masui K;Li B;Zhu S;Gu Y;Villa GR;Akhavan D;Nathanson D;Gini B;Mareninov S;Li R;Camacho CE;Kurdistani SK;Eskin A;Nelson SF;Yong WH;Cavenee WK;Cloughesy TF;Christofk HR;Black DL;Mischel PS
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影响因子：
4.8
作者：
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通讯作者：
Guyer, CA
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7.8
作者：
CARPENTIER, JL;GORDEN, P;ORCI, L
通讯作者：
ORCI, L
影响因子：
4.3
作者：
Bollu, Lakshmi Reddy;Ren, Jiangong;Zhang Weihua
通讯作者：
Zhang Weihua
影响因子：
5.3
作者：
Boerner, JL;Demory, ML;Parsons, SJ
通讯作者：
Parsons, SJ