Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells

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Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells. / Staberg, Mikkel; Riemer, Christian; Xu, Ruodan; Dmytriyeva, Oksana; Bock, Elisabeth; Berezin, Vladimir.

I: Cellular Oncology, Bind 36, Nr. 3, 06.2013, s. 201-11.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Staberg, M, Riemer, C, Xu, R, Dmytriyeva, O, Bock, E & Berezin, V 2013, 'Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells', Cellular Oncology, bind 36, nr. 3, s. 201-11. https://doi.org/10.1007/s13402-013-0128-6

APA

Staberg, M., Riemer, C., Xu, R., Dmytriyeva, O., Bock, E., & Berezin, V. (2013). Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells. Cellular Oncology, 36(3), 201-11. https://doi.org/10.1007/s13402-013-0128-6

Vancouver

Staberg M, Riemer C, Xu R, Dmytriyeva O, Bock E, Berezin V. Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells. Cellular Oncology. 2013 jun;36(3):201-11. https://doi.org/10.1007/s13402-013-0128-6

Author

Staberg, Mikkel ; Riemer, Christian ; Xu, Ruodan ; Dmytriyeva, Oksana ; Bock, Elisabeth ; Berezin, Vladimir. / Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells. I: Cellular Oncology. 2013 ; Bind 36, Nr. 3. s. 201-11.

Bibtex

@article{15bf73d5b7ca4896b33560e9769d9fac,
title = "Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells",
abstract = "BACKGROUND: Receptors of the ErbB family are involved in the development of various cancers, and the inhibition of these receptors represents an attractive therapeutic concept. Upon ligand binding, ErbB receptors become activated as homo- or heterodimers, leading to the activation of downstream signaling cascades that result in the facilitation of cell proliferation and migration. A region of the extracellular part of the receptor, termed the 'dimerization arm', is important for the formation of receptor dimers and represents an attractive target for the design of ErbB inhibitors.METHODS: An ErbB1 targeting peptide, termed Herfin-1, was designed based on a model of the tertiary structure of the EGF-EGFR ternary complex. The binding kinetics of this peptide were determined employing surface plasmon resonance analyses. ErbB1-4 expression and phosphorylation in human glioblastoma cell lines U87 and U118 were determined by Western blotting using specific antibodies. Cell proliferation was determined by MTS staining. Cell migration was examined using a Chemotaxis Migration Kit. Neurite outgrowth from primary cerebellar granule neurons was evaluated by fluorescence microscopy and image processing.RESULTS: The present study shows that Herfin-1 functions as an ErbB1 antagonist. It binds to the extracellular domain of ErbB1 with a KD value of 361 nM. In U87 and U118 cells, both expressing high levels of ErbB1, Herfin-1 inhibits EGF-induced ErbB1 phosphorylation and cell migration. Additionally, Herfin-1 was found to increase neurite outgrowth in cerebellar granule neurons, likely through the inhibition of a sustained weak ErbB1 activation.CONCLUSIONS: Targeting the ErbB1 receptor dimerization interface is a promising strategy to inhibit receptor activation in ErbB1-expressing glioma cells.",
keywords = "Amino Acid Sequence, Animals, Brain Neoplasms, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cells, Cultured, Drug Design, Epidermal Growth Factor, Glioblastoma, Humans, Molecular Sequence Data, Neurites, Neurogenesis, Peptides, Phosphorylation, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Rats, Rats, Wistar, Receptor, Epidermal Growth Factor",
author = "Mikkel Staberg and Christian Riemer and Ruodan Xu and Oksana Dmytriyeva and Elisabeth Bock and Vladimir Berezin",
year = "2013",
month = "6",
doi = "10.1007/s13402-013-0128-6",
language = "English",
volume = "36",
pages = "201--11",
journal = "Cellular Oncology",
issn = "2211-3428",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells

AU - Staberg, Mikkel

AU - Riemer, Christian

AU - Xu, Ruodan

AU - Dmytriyeva, Oksana

AU - Bock, Elisabeth

AU - Berezin, Vladimir

PY - 2013/6

Y1 - 2013/6

N2 - BACKGROUND: Receptors of the ErbB family are involved in the development of various cancers, and the inhibition of these receptors represents an attractive therapeutic concept. Upon ligand binding, ErbB receptors become activated as homo- or heterodimers, leading to the activation of downstream signaling cascades that result in the facilitation of cell proliferation and migration. A region of the extracellular part of the receptor, termed the 'dimerization arm', is important for the formation of receptor dimers and represents an attractive target for the design of ErbB inhibitors.METHODS: An ErbB1 targeting peptide, termed Herfin-1, was designed based on a model of the tertiary structure of the EGF-EGFR ternary complex. The binding kinetics of this peptide were determined employing surface plasmon resonance analyses. ErbB1-4 expression and phosphorylation in human glioblastoma cell lines U87 and U118 were determined by Western blotting using specific antibodies. Cell proliferation was determined by MTS staining. Cell migration was examined using a Chemotaxis Migration Kit. Neurite outgrowth from primary cerebellar granule neurons was evaluated by fluorescence microscopy and image processing.RESULTS: The present study shows that Herfin-1 functions as an ErbB1 antagonist. It binds to the extracellular domain of ErbB1 with a KD value of 361 nM. In U87 and U118 cells, both expressing high levels of ErbB1, Herfin-1 inhibits EGF-induced ErbB1 phosphorylation and cell migration. Additionally, Herfin-1 was found to increase neurite outgrowth in cerebellar granule neurons, likely through the inhibition of a sustained weak ErbB1 activation.CONCLUSIONS: Targeting the ErbB1 receptor dimerization interface is a promising strategy to inhibit receptor activation in ErbB1-expressing glioma cells.

AB - BACKGROUND: Receptors of the ErbB family are involved in the development of various cancers, and the inhibition of these receptors represents an attractive therapeutic concept. Upon ligand binding, ErbB receptors become activated as homo- or heterodimers, leading to the activation of downstream signaling cascades that result in the facilitation of cell proliferation and migration. A region of the extracellular part of the receptor, termed the 'dimerization arm', is important for the formation of receptor dimers and represents an attractive target for the design of ErbB inhibitors.METHODS: An ErbB1 targeting peptide, termed Herfin-1, was designed based on a model of the tertiary structure of the EGF-EGFR ternary complex. The binding kinetics of this peptide were determined employing surface plasmon resonance analyses. ErbB1-4 expression and phosphorylation in human glioblastoma cell lines U87 and U118 were determined by Western blotting using specific antibodies. Cell proliferation was determined by MTS staining. Cell migration was examined using a Chemotaxis Migration Kit. Neurite outgrowth from primary cerebellar granule neurons was evaluated by fluorescence microscopy and image processing.RESULTS: The present study shows that Herfin-1 functions as an ErbB1 antagonist. It binds to the extracellular domain of ErbB1 with a KD value of 361 nM. In U87 and U118 cells, both expressing high levels of ErbB1, Herfin-1 inhibits EGF-induced ErbB1 phosphorylation and cell migration. Additionally, Herfin-1 was found to increase neurite outgrowth in cerebellar granule neurons, likely through the inhibition of a sustained weak ErbB1 activation.CONCLUSIONS: Targeting the ErbB1 receptor dimerization interface is a promising strategy to inhibit receptor activation in ErbB1-expressing glioma cells.

KW - Amino Acid Sequence

KW - Animals

KW - Brain Neoplasms

KW - Cell Line, Tumor

KW - Cell Movement

KW - Cell Proliferation

KW - Cells, Cultured

KW - Drug Design

KW - Epidermal Growth Factor

KW - Glioblastoma

KW - Humans

KW - Molecular Sequence Data

KW - Neurites

KW - Neurogenesis

KW - Peptides

KW - Phosphorylation

KW - Protein Binding

KW - Protein Structure, Secondary

KW - Protein Structure, Tertiary

KW - Rats

KW - Rats, Wistar

KW - Receptor, Epidermal Growth Factor

U2 - 10.1007/s13402-013-0128-6

DO - 10.1007/s13402-013-0128-6

M3 - Journal article

VL - 36

SP - 201

EP - 211

JO - Cellular Oncology

JF - Cellular Oncology

SN - 2211-3428

IS - 3

ER -

ID: 118389661