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ErbB/EGF Signaling and EMT in Mammary Development and Breast Cancer

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Activation of the ErbB family of receptor tyrosine kinases via cognate Epidermal Growth Factor (EGF)-like peptide ligands constitutes a major group of related signaling pathways that control proliferation, survival, angiogenesis and metastasis of breast cancer. In this respect, clinical trials with various ErbB receptor blocking antibodies and specific tyrosine kinase inhibitors have proven to be partially efficacious in the treatment of this heterogeneous disease. Induction of an embryonic program of epithelial-to-mesenchymal transition (EMT) in breast cancer, whereupon epithelial tumor cells convert to a more mesenchymal-like phenotype, facilitates the migration, intravasation, and extravasation of tumor cells during metastasis. Breast cancers which exhibit properties of EMT are highly aggressive and resistant to therapy. Activation of ErbB signaling can regulate EMT-associated invasion and migration in normal and malignant mammary epithelial cells, as well as modulating discrete stages of mammary gland development. The purpose of this review is to summarize current information regarding the role of ErbB signaling in aspects of EMT that influence epithelial cell plasticity during mammary gland development and tumorigenesis. How this information may contribute to the improvement of therapeutic approaches in breast cancer will also be addressed.

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Abbreviations

EGF:

Epidermal Growth Factor

EGFR:

Epidermal Growth Factor Receptor

EMT:

Epithelial-to-mesenchymal transition

MET:

Mesenchymal-to-epithelial transition

RTK:

Receptor tyrosine kinase

TGFα:

Transforming Growth Factor-α

TGFβ:

Transforming Growth Factor-β

EGF-CFC:

Epidermal Growth Factor-Cripto-1/FRL-1/Cryptic

AREG:

Amphiregulin

NRG1:

Neuregulin-1

NRG3:

Neuregulin-3

HB-EGF:

Heparin-Binding EGF-like Growth Factor

AV:

Atrioventricular

HA:

Hyaluronic acid

ska:

Scaramanga

ECM:

Extracellular matrix

MMP:

Matrix Metalloprotease

TEB:

Terminal end bud

ADAM17:

A Disintegrin and Metalloproteinase-17

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Correspondence to Luigi Strizzi.

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This work is supported by the U.S. National Institutes of Health (NIH) intramural funding, NIH extramural grants (CA59702 and CA121205) and the Eisenberg Scholar Research Award. We apologize to authors whose work was not mentioned directly.

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Hardy, K.M., Booth, B.W., Hendrix, M.J.C. et al. ErbB/EGF Signaling and EMT in Mammary Development and Breast Cancer. J Mammary Gland Biol Neoplasia 15, 191–199 (2010). https://doi.org/10.1007/s10911-010-9172-2

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