Investigations of EGFR configurations on tumor cell surface by high-resolution electron microscopy

被引:5
作者
Wang, Li [1 ]
Li, Jintao [2 ]
Zhang, Na [2 ]
Zhang, Xiaofei [1 ]
Xia, Yang [2 ]
Chai, Binbin [2 ]
Gao, Chunlang [1 ]
Mao, Shengcheng [1 ]
Ji, Yuan [1 ]
Sheng, Wang [2 ]
Han, Xiaodong [1 ]
机构
[1] Beijing Univ Technol, Inst Microstruct & Property Adv Mat, Beijing Key Lab Microstruct & Properties Solids, Beijing 100124, Peoples R China
[2] Beijing Univ Technol, Cooperat Base Antivirus Drug, Beijing Key Lab Environm & Viral Oncol, Coll Life Sci & Bioengn,Beijing Int Sci & Technol, Beijing 100124, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
EGFR; Configuration; Oligomerization; TEM; SEM; Structural model; EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR EGFR; CRYSTAL-STRUCTURE; ACTIVATION; EXPRESSION; AFFINITY; LIMIT;
D O I
10.1016/j.bbrc.2020.07.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epidermal growth factor receptor (EGFR) is an important target for tumor therapy in various tumors. The current understanding of EGFR conformations on the cell surface is based on X-ray structural data, molecular dynamic simulations, and fluorescence-localization imaging. Using scanning electron microscope (SEM) and transmission electron microscope (TEM) with the resolution at sub-nanometers, we successfully recognized individual molecules of EGFRs and their assembly details on the surface of triple-negative breast cancer (TNBC) upon one-to-one labeling by Au nanoparticles. Based on our results, we have proposed the possible configurations, structural models, and conformational transitions of EGFR oligomers. Our study shows that the high-resolution electron imaging is an invaluable tool to provide direct evidence of EGFR configuration on tumor cell surfaces, and may play a pivotal role in further understanding of EGFR-associated signaling and tumor therapy. (C) 2020 Elsevier Inc. All rights reserved.
引用
收藏
页码:179 / 184
页数:6
相关论文
共 31 条
[1]   An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors [J].
Burgess, AW ;
Cho, HS ;
Eigenbrot, C ;
Ferguson, KM ;
Garrett, TPJ ;
Leahy, DJ ;
Lemmon, MA ;
Sliwkowski, MX ;
Ward, CW ;
Yokoyama, S .
MOLECULAR CELL, 2003, 12 (03) :541-552
[2]   Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor α [J].
Garrett, TPJ ;
McKern, NM ;
Lou, MZ ;
Elleman, TC ;
Adams, TE ;
Lovrecz, GO ;
Zhu, HJ ;
Walker, F ;
Frenkel, MJ ;
Hoyne, PA ;
Jorissen, RN ;
Nice, EC ;
Burgess, AW ;
Ward, CW .
CELL, 2002, 110 (06) :763-773
[3]   Prerequisites for a Cc/Cs-corrected ultrahigh-resolution TEM [J].
Haider, M. ;
Mueller, H. ;
Uhlemann, S. ;
Zach, J. ;
Loebau, U. ;
Hoeschen, R. .
ULTRAMICROSCOPY, 2008, 108 (03) :167-178
[4]   BREAKING THE DIFFRACTION RESOLUTION LIMIT BY STIMULATED-EMISSION - STIMULATED-EMISSION-DEPLETION FLUORESCENCE MICROSCOPY [J].
HELL, SW ;
WICHMANN, J .
OPTICS LETTERS, 1994, 19 (11) :780-782
[5]   Nanoparticle-mediated cellular response is size-dependent [J].
Jiang, Wen ;
Kim, Betty Y. S. ;
Rutka, James T. ;
Chan, Warren C. W. .
NATURE NANOTECHNOLOGY, 2008, 3 (03) :145-150
[6]   CHICKEN EPIDERMAL GROWTH-FACTOR (EGF) RECEPTOR - CDNA CLONING, EXPRESSION IN MOUSE CELLS, AND DIFFERENTIAL BINDING OF EGF AND TRANSFORMING GROWTH FACTOR-ALPHA [J].
LAX, I ;
JOHNSON, A ;
HOWK, R ;
SAP, J ;
BELLOT, F ;
WINKLER, M ;
ULLRICH, A ;
VENNSTROM, B ;
SCHLESSINGER, J ;
GIVOL, D .
MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (05) :1970-1978
[7]   The EGFR Family: Not So Prototypical Receptor Tyrosine Kinases [J].
Lemmon, Mark A. ;
Schlessinger, Joseph ;
Ferguson, Kathryn M. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2014, 6 (04)
[8]   Cell Signaling by Receptor Tyrosine Kinases [J].
Lemmon, Mark A. ;
Schlessinger, Joseph .
CELL, 2010, 141 (07) :1117-1134
[9]   Mechanisms for Kinase-mediated Dimerization of the Epidermal Growth Factor Receptor [J].
Lu, Chafen ;
Mi, Li-Zhi ;
Schuerpf, Thomas ;
Walz, Thomas ;
Springer, Timothy A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (45) :38244-38253
[10]   Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain [J].
Moriki, T ;
Maruyama, H ;
Maruyama, IN .
JOURNAL OF MOLECULAR BIOLOGY, 2001, 311 (05) :1011-1026