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A novel functional crosstalk between DDR1 and the IGF axis and its relevance for breast cancer
Belfiore, Antonino Malaguarnera, Roberta Nicolosi, Maria Luisa Lappano, Rosamaria Ragusa, Marco Vella, Veronica
Belfiore, Antonino
Malaguarnera, Roberta
Nicolosi, Maria Luisa
Lappano, Rosamaria
Ragusa, Marco
Vella, Veronica
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Journal article
Date
2018-03-23
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Biology
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https://doi.org/10.1080/19336918.2018.1445953
Abstract
In the last decades increasing importance has been attributed to the Insulin/Insulin-like Growth Factor signaling (IIGFs) in cancer development, progression and resistance to therapy. In fact, IIGFs is often deregulated in cancer. In particular, the mitogenic insulin receptor isoform A (IR-A) and the insulin-like growth factor receptor (IGF-1R) are frequently overexpressed in cancer together with their cognate ligands IGF-1 and IGF-2. Recently, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein. DDR1, a non-integrin collagen tyrosine kinase receptor, is overexpressed in several malignancies and plays a role in cancer progression and metastasis. Herein, we review recent findings indicating that DDR1 is as a novel modulator of IR and IGF-1R expression and function. DDR1 functionally interacts with IR and IGF-1R and enhances the biological actions of insulin, IGF-1 and IGF-2. Conversely, DDR1 is upregulated by IGF-1, IGF-2 and insulin through the PI3K/AKT/miR-199a-5p circuit. Furthermore, we discuss the role of the non-canonical estrogen receptor GPER1 in the DDR1-IIGFs crosstalk. These data suggest a wider role of DDR1 as a regulator of cell response to hormones, growth factors, and signals coming from the extracellular matrix.
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Antonino Belfiore, Roberta Malaguarnera, Maria Luisa Nicolosi, Rosamaria Lappano, Marco Ragusa, Andrea Morrione & Veronica Vella (2018) A novel functional crosstalk between DDR1 and the IGF axis and its relevance for breast cancer, Cell Adhesion & Migration, 12:4, 305-314, DOI: 10.1080/19336918.2018.1445953
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Cell Adhesion & Migration, Vol. 12, No. 4
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