A novel functional crosstalk between DDR1 and the IGF axis and its relevance for breast cancer

Cell Adhesion & Migration
Antonino BelfioreVeronica Vella

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 ...Continue Reading

References

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Jul 26, 2003·The Journal of Biological Chemistry·Giuseppe PandiniAntonino Belfiore
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Feb 20, 2014·Frontiers in Endocrinology·Roberta Malaguarnera, Antonino Belfiore
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Sep 29, 2015·Oncotarget·Damiano Cosimo RigiraccioloErnestina Marianna De Francesco
Oct 4, 2017·Endocrine Reviews·Antonino BelfioreRiccardo Vigneri

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Citations

Oct 12, 2019·Cells·Caitrin CruddenLeonard Girnita
Jun 18, 2020·Journal of Cellular and Molecular Medicine·Qi ZhangYing Lin
Jul 4, 2018·Cell Adhesion & Migration·Birgit Leitinger, Frédéric Saltel
Dec 6, 2018·International Journal of Molecular Sciences·Veronica Vella, Roberta Malaguarnera
Nov 30, 2019·Biomolecules·Kathleen Wantoch von RekowskiGerd Bendas
Nov 21, 2018·International Journal of Molecular Sciences·Veronica VellaLaura Sciacca
Aug 9, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Veronica VellaAntonino Belfiore
Feb 27, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·V MehtaA Munshi
Mar 7, 2021·Biomolecules·Caterina MancarellaKatia Scotlandi
Nov 9, 2021·Frontiers in Big Data·Domenico SgarigliaFabricio Alves Barbosa da Silva

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Methods Mentioned

BETA
ubiquitination
transfection

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