NDLI: A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo

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A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo

Content Provider	PubMed Central
Author	Xu, Ruodan Povlsen, Gro Klitgaard Soroka, Vladislav Bock, Elisabeth Berezin, Vladimir
Copyright Year	2010
Abstract	The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in tumorigenesis and cancer disease progression, and therefore has become an attractive target for structure-based drug design. ErbB receptors are activated by ligand-induced homo- and heterodimerization. Structural studies have revealed that ErbB receptor dimers are stabilized by receptor–receptor interactions, primarily mediated by a region in the second extracellular domain, termed the “dimerization arm”. The present study is the first biological characterization of a peptide, termed Inherbin3, which constitutes part of the dimerization arm of ErbB3. Inherbin3 binds to the extracellular domains of all four ErbB receptors, with the lowest peptide binding affinity for ErbB4. Inherbin3 functions as an antagonist of epidermal growth factor (EGF)-ErbB1 signaling. We show that Inherbin3 inhibits EGF-induced ErbB1 phosphorylation, cell growth, and migration in two human tumor cell lines, A549 and HN5, expressing moderate and high ErbB1 levels, respectively. Furthermore, we show that Inherbin3 inhibits tumor growth in vivo and induces apoptosis in a tumor xenograft model employing the human non-small cell lung cancer cell line A549. The Inherbin3 peptide may be a useful tool for investigating the mechanisms of ErbB receptor homo- and heterodimerization. Moreover, the here described biological effects of Inherbin3 suggest that peptide-based targeting of ErbB receptor dimerization is a promising anti-cancer therapeutic strategy.
Related Links	http://dx.doi.org/10.3233/CLO-2010-0515
Starting Page	259
File Format	PDF
ISSN	18758606
e-ISSN	18758606
Journal	Cellular Oncology : the Official Journal of the International Society for Cellular Oncology
Issue Number	4
Volume Number	32
Language	English
Publisher	IOS Press
Publisher Date	2010-01-01
Access Restriction	Open
Rights Holder	IOS Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Molecular Medicine Oncology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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