Eph受体家族在肺癌中的研究进展及作为肺癌治疗靶点的可能

doi:10.11904/j.issn.1002-3070.2018.02.015

摘要/Abstract

摘要： Eph受体及其膜结合型配体Ephrin与血管发生、细胞迁移、神经元定位、胚胎发育等密切相关,越来越多的研究表明它们参与各种癌症的发生和发展。本文重点讨论Eph受体家族参与肺癌组织形成和发展,以及转移、耐药等方面的机制,及其作为肺癌靶向治疗靶点的可能性。

关键词: Eph, Ephrin, 肺癌

Abstract: The Eph receptors and their ligand Ephrins are closely associated with angiogenesis,cell migration,neuronal localization and embryonic development.More and more studies have shown that the Eph receptor and Ephrins are involved in the occurrence and development of various cancers.In this article,we will focus on the Eph receptor family involved in the formation and development of lung cancer and metastasis,drug resistance and other mechanisms as well as their potential as targeted therapy of lung cancer.

Key words: Eph, Ephrin, Lung cancer

中图分类号:

R734.2

何佳雯, 陈公琰. Eph受体家族在肺癌中的研究进展及作为肺癌治疗靶点的可能[J]. 实用肿瘤学杂志, 2018, 32(2): 164-168.

HE Jiawen, CHEN Gongyan. Research progress of Eph receptor family in the lung cancer and its potential application as targets of lung cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(2): 164-168.

参考文献

1 Siegel R,Ward E,Brawley O,et al.Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths[J].Ca:A Cancer J Clin,2011,61(4):212-236.
2 Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA:A Cancer J Clin,2016,66(2):115.
3 Yamagata N,Shyr Y,Yanagisawa K,et al.A training-testing approach to the molecular classification of resected non-small cell lung cancer[J].Clin Cancer Res,2003,9(13):4695-4704.
4 Janes PW,Nievergall E,Lackmann M.Concepts and consequences of Eph receptor clustering[J].Semin Cell Dev Biol,2012,23(1):43-50.
5 Himanen JP.Ectodomain structures of Eph receptors[J].Semin Cell Dev Biol,2012,23(1):35.
6 Flanagan JVP.The Ephrins and Eph receptors in neural development[J].Annu Rev Neurosci,1998,21(21):309.
7 Greenman C,Stephens P,Smith R,et al.Patterns of somatic mutation in human cancer genomes[J].Nature,2007,446(7132):153.
8 Davies H,Hunter C,Smith R,et al.Somatic mutations of the protein kinase gene family in human lung cancer[J].Cancer Res,2005,65(17):7591.
9 Ding L,Getz G,Wheeler DA,et al.Somatic mutations affect key pathways in lung adenocarcinoma[J].Nature,2008,455(7216):1069-1075.
10 Wood LD,Calhoun ES,Silliman N,et al.Somatic mutations of GUCY2F,EphA3,and NTRK3 in human cancers[J].Hum Mut,2006,27(10):1060.
11 Lisabeth EM,Fernandez C,Pasquale EB.Cancer somatic mutations disrupt functions of the EphA3 receptor tyrosine kinase through multiple mechanisms[J].Biochemistry,2012,51(7):1464-1475.
12 Brannan JM,Dong W,Prudkin L,et al.Expression of the receptor tyrosine kinase EphA2 is increased in smokers and predicts poor survival in non-small cell lung cancer[J].Clin Cancer Res,2009,15(13):4423-4430.
13 Faoro L,Singleton PA,Cervantes GM,et al.EphA2 mutation in lung squamous cell carcinoma promotes increased cell survival,cell invasion,focal adhesions,and mammalian target of rapamycin activation[J].J Biol Chem,2010,285(24):18575.
14 Macrae M,Neve RM,Rodriguezviciana P,et al.A conditional feedback loop regulates Ras activity through EphA2[J].Cancer Cell,2005,8(2):111-118.
15 Larsen A,Pedersen MM,Grandal M,et al.Activation of the EGFR gene target EphA2 inhibits epidermal growth factor-induced cancer cell motility[J].Mol Cancer Res,2007,5(3):283-293.
16 Kullander K,Klein R.Mechanisms and functions of Eph and Ephrin signalling[J].Nat Rev Mol Cell Biol,2002,3(7):475.
17 Nasreen N,Mohammed KA,Lai Y,et al.Receptor EphA2 activation with EphrinA1 suppresses growth of malignant mesothelioma(MM)[J].Cancer Lett,2007,258(2):215-222.
18 Lee HY,Mohammed KA,Peruvemba S,et al.Targeted lung cancer therapy using EphrinA1-loaded albumin microspheres[J].J Pharm Pharmacol,2011,63(11):1401-1410.
19 Ji XD,Li G,Feng YX,et al.EphB3 is overexpressed in non-small-cell lung cancer and promotes tumor metastasis by enhancing cell survival and migration[J].Cancer Res,2011,71(3):1156-1166.
20 Guo L,Ji XD,Hong G,et al.EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex[J].Nat Commun,2012,3(2):667.
21 Kumar SR,Singh J,Xia G,et al.Receptor tyrosine kinase EphB4 is a survival factor in breast cancer[J].Am J Pathol,2006,169(1):279-293.
22 Noren NK,Foos G,Hauser CA,et al.The EphB4 receptor suppresses breast cancer cell tumorigenicity through an Abl-Crk pathway[J].Nat Cell Biol,2006,8(8):815.
23 Miao H,Li DQ,Mukherjee A,et al.EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt[J].Cancer Cell,2009,16(1):9-20.
24 Favre CJ,Mancuso M,Maas K,et al.Expression of genes involved in vascular development and angiogenesis in endothelial cells of adult lung[J].Am J Physiol Heart Circ Physiol,2003,285(5):1917.
25 Wang Y,Nakayama M,Pitulescu ME,et al.Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis[J].Nature,2010,465(7297):483-486.
26 Yamanda S,Ebihara S,Asada M,et al.Role of EphrinB2 in nonproductive angiogenesis induced by Delta-like 4 blockade[J].Blood,2009,113(15):3631-3639.
27 Mcnally L,Manne U,Grizzle WE.Post-transcriptional processing of genetic information and its relation to cancer[J].Biotech Histochem,2013,88(7):365.
28 Peng J,Wang Q,Liu H,et al.EphA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway[J].Tumour Biol,2016,37(9):11959.
29 Suzuki M,Abe A,Imagama S,et al.BCR-ABL-independent and RAS/MAPK pathway-dependent form of imatinib resistance in Ph-positive acute lymphoblastic leukemia cell line with activation of EphB4[J].Eur J Haematol,2010,84(3):229-238.
30 Ding L,Shen Y,Ni J,et al.EphA4 promotes cell proliferation and cell adhesion-mediated drug resistance via the AKT pathway in multiple myeloma[J].Tumour Biol,2017,39(3):1010428317694298.
31 Huang F,Reeves K,Han X,et al.Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib:rationale for patient selection[J].Cancer Res,2007,67(5):2226-2238.
32 Li J,Rix U,Fang B,et al.A chemical and phosphoproteomic characterization of dasatinib action in lung cancer[J].Nat Chem Biol,2010,6(4):291.
33 Johnson FM,Bekele BN,Feng L,et al.Phase II study of dasatinib in patients with advanced non-small-cell lung cancer[J].J Clin Oncol,2010,28(30):4609.
34 Pietanza MC,Gadgeel SM,Dowlati A,et al.Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer[J].J Thorac Oncol,2012,7(5):856-865.
35 Day BW,Stringer BW,Alejeh F,et al.EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme[J].Cancer Cell,2013,23(2):238-248.
36 Hughes A,Clarson J,Gargett T,et al.Comment on "KB004,a first in class monoclonal antibody targeting the receptor tyrosine kinase EphA3,in patients with advanced hematologic malignancies:Results from a phase 1 study"[J].Leuk Res,2017,55-57.

[1]	张佳文,于雁,张薇,曹京燕,罗雯,尚利华. 基于UPLC-TOF/MS的小细胞肺癌患者血清代谢组学研究[J]. 实用肿瘤学杂志, 2019, 33(3): 200-205.
[2]	孙立春,李丹丹,李净,于凤玲. CCDC8和TGF-β1在非小细胞肺癌中的表达及临床意义[J]. 实用肿瘤学杂志, 2019, 33(3): 215-221.
[3]	刘志强,褚艳杰,刘静,王彦博. m白术内酯Ⅰ通过TLR4/MyD88通路调控肺癌A549细胞增殖侵袭的研究[J]. 实用肿瘤学杂志, 2019, 33(3): 228-232.
[4]	张彦秋,韩阿蒙,李金旺,顾涛,付占昭,毛羽,张子健,杨振. CRT+ARC技术在局部晚期肺癌患者中临床应用的初步研究[J]. 实用肿瘤学杂志, 2019, 33(3): 256-260.
[5]	赵苏, 郑晓瑜, 朱开彬, 卜建龙, 徐世东. 肺癌完全性切除术对患者外周血中Th17/Treg细胞平衡的影响[J]. 实用肿瘤学杂志, 2019, 33(2): 142-148.
[6]	陈冲, 王建, 杨帅. miR-129通过靶向SEPHS1对骨肉瘤细胞MG-63增殖及凋亡的影响[J]. 实用肿瘤学杂志, 2019, 33(1): 21-26.
[7]	胡智慧综述, 张静审校. SNP对放射性肺损伤预测作用的研究进展[J]. 实用肿瘤学杂志, 2019, 33(1): 87-91.
[8]	迪娜·木拉力, 胡昕综述, 加孜那·托哈依审校. 远程医疗在肺癌中的应用及前景[J]. 实用肿瘤学杂志, 2018, 32(6): 555-557.
[9]	李万祯, 殷俊, 李萍, 林晓辉, 张国前, 张书旭. iR-17在非小细胞肺癌放射抗拒细胞中的表达及作用研究[J]. 实用肿瘤学杂志, 2018, 32(5): 391-397.
[10]	蔡静, 候玥. 非小细胞肺癌患者血清miR-195的表达及其临床意义[J]. 实用肿瘤学杂志, 2018, 32(5): 415-419.
[11]	钟雪莱, 杨海粒, 王国年. 不同麻醉方式对老年肺癌患者术后认知功能的影响[J]. 实用肿瘤学杂志, 2018, 32(5): 432-436.
[12]	朱晓云, 张亚宁, 林菲, 马碧萍. 上海市金山区2002-2013年肺癌发病及死亡分析[J]. 实用肿瘤学杂志, 2018, 32(5): 437-441.
[13]	崔晓燕, 涂青, 甘建辉. 纳布啡与羟考酮自控镇痛对非小细胞肺癌患者术后免疫因子水平影响的比较[J]. 实用肿瘤学杂志, 2018, 32(4): 309-314.
[14]	魏静, 陶媛美慧, 付英梅, 赵吉子, 张文莉, 张凤民. 肺结核与肺癌相互影响的研究进展[J]. 实用肿瘤学杂志, 2018, 32(4): 340-343.
[15]	雷俊华, 许冠华, 曾江正, 黄芬, 何志惠, 卢彦达. 隐丹参酮联合顺铂抗非小细胞肺癌NCI-H1975细胞JAK2/STAT3机制研究[J]. 实用肿瘤学杂志, 2018, 32(3): 198-202.