ErbB/EGF signaling and EMT in mammary development and breast cancer.
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.
Hardy
Katharine M
KM
Children's Memorial Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 2300 Children's Plaza, Chicago, IL 60614, USA.
Booth
Brian W
BW
Hendrix
Mary J C
MJ
Salomon
David S
DS
Strizzi
Luigi
L
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D047108:Embryonic Development; D004815:Epidermal Growth Factor / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D008321:Mammary Glands, Animal / Q000196:embryology / Q000502:physiology / Q000503:physiopathology; D042361:Mammary Glands, Human / Q000196:embryology / Q000502:physiology* / Q000503:physiopathology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D008024:Ligands; D004815:Epidermal Growth Factor; D020794:Receptor Protein-Tyrosine Kinases