Insulin/IGF signaling and discoidin domain receptors: An emerging functional connection

The insulin/insulin-like growth factor system (IIGFs) plays a fundamental role in the regulation of prenatal and postnatal growth, metabolism and homeostasis. As a consequence, dysregulation of this axis is associated with growth disturbance, type 2 diabetes, chronic inflammation and tumor progressi...

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Published in:Biochimica et biophysica acta. Molecular cell research 2019-11, Vol.1866 (11), p.118522-118522, Article 118522
Main Authors: Vella, Veronica, Malaguarnera, Roberta, Nicolosi, Maria Luisa, Morrione, Andrea, Belfiore, Antonino
Format: Article
Language:English
Subjects:
Animals
Breast cancer
DDR1
DDR2
Diabetes Mellitus, Type 2
Discoidin Domain Receptor 1 - metabolism
Discoidin Domain Receptor 2 - metabolism
Discoidin domain receptors
Discoidin Domain Receptors - metabolism
Fibrosis
Humans
Inflammation
Insulin - metabolism
Insulin receptor
Insulin-Like Growth Factor II - metabolism
Insulin-like growth factor system
Insulin-like growth factor-2
Isoform A
Neoplasms - metabolism
Phosphorylation
Protein Binding
Protein Isoforms
Receptor, Insulin
Receptors, Somatomedin
Signal Transduction
Somatomedins - metabolism
Thyroid cancer
Thyroid Neoplasms - metabolism
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Summary:The insulin/insulin-like growth factor system (IIGFs) plays a fundamental role in the regulation of prenatal and postnatal growth, metabolism and homeostasis. As a consequence, dysregulation of this axis is associated with growth disturbance, type 2 diabetes, chronic inflammation and tumor progression. A functional crosstalk between IIGFs and discoidin domain receptors (DDRs) has been recently discovered. DDRs are non-integrin collagen receptors that canonically undergo slow and long-lasting autophosphorylation after binding to fibrillar collagen. While both DDR1 and DDR2 functionally interact with IIGFs, the crosstalk with DDR1 is so far better characterized. Notably, the IIGFs-DDR1 crosstalk presents a feed-forward mechanism, which does not require collagen binding, thus identifying novel non-canonical action of DDR1. Further studies are needed to fully explore the role of this IIGFs-DDRs functional loop as potential target in the treatment of inflammatory and neoplastic disorders. [Display omitted] •DDR1 and IIGFs are linked by a functional feed-forward loop.•DDR1 inhibition reduces IIGFs protumorigenic actions and favors cancer differentiation.•DDR1 crosstalk with IIGFs does not require collagen binding.
ISSN:0167-4889
1879-2596
DOI:10.1016/j.bbamcr.2019.118522