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Title: Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

Abstract

Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
Life Sciences Division
OSTI Identifier:
986245
Report Number(s):
LBNL-3804E
Journal ID: 0036-8075; TRN: US201017%%163
DOE Contract Number:  
DE-AC02-05CH11231; U54 CA143836, P50 CA 58207, U54 CA 112970
Resource Type:
Journal Article
Resource Relation:
Journal Name: Science; Journal Volume: 327; Journal Issue: 5971; Related Information: Journal Publication Date: March 12, 2010
Country of Publication:
United States
Language:
English
Subject:
59; FUNCTIONALS; GEOMETRY; MAMMARY GLANDS; MEMBRANES; MORPHOLOGY; NEOPLASMS; PHOSPHOTRANSFERASES; REGULATIONS; TRANSPORT; TYROSINE

Citation Formats

Salaita, Khalid, Nair, Pradeep M, Petit, Rebecca S, Neve, Richard M, Das, Debopriya, Gray, Joe W, and Groves, Jay T. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2. United States: N. p., 2009. Web.
Salaita, Khalid, Nair, Pradeep M, Petit, Rebecca S, Neve, Richard M, Das, Debopriya, Gray, Joe W, & Groves, Jay T. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2. United States.
Salaita, Khalid, Nair, Pradeep M, Petit, Rebecca S, Neve, Richard M, Das, Debopriya, Gray, Joe W, and Groves, Jay T. Wed . "Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2". United States. doi:. https://www.osti.gov/servlets/purl/986245.
@article{osti_986245,
title = {Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2},
author = {Salaita, Khalid and Nair, Pradeep M and Petit, Rebecca S and Neve, Richard M and Das, Debopriya and Gray, Joe W and Groves, Jay T},
abstractNote = {Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.},
doi = {},
journal = {Science},
number = 5971,
volume = 327,
place = {United States},
year = {Wed Sep 09 00:00:00 EDT 2009},
month = {Wed Sep 09 00:00:00 EDT 2009}
}