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

Antonino Belfiore1, Roberta Malaguarnera2, Maria Luisa Nicolosi2

  • 1a Endocrinology, Department of Clinical and Experimental Medicine , University of Catania, Garibaldi-Nesima Hospital , Catania , Italy.

Cell Adhesion & Migration
|March 1, 2018
PubMed

Insights

Discoidin domain receptor 1 (DDR1) interacts with insulin/IGF signaling pathways, modulating cancer growth and therapy resistance. DDR1 is upregulated by these signals, highlighting its role in hormone and growth factor response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Insulin/Insulin-like Growth Factor signaling (IIGFs) is crucial in cancer development, progression, and therapy resistance.
  • Insulin receptor isoform A (IR-A) and IGF-1 receptor (IGF-1R) are frequently overexpressed in cancers.
  • Discoidin domain receptor 1 (DDR1), a collagen tyrosine kinase receptor, is implicated in cancer progression and metastasis.

Purpose of the Study:

  • To review recent findings on DDR1 as a novel modulator of IR and IGF-1R expression and function.
  • To elucidate the functional interaction between DDR1 and IIGFs pathways.
  • To discuss the role of GPER1 in the DDR1-IIGFs crosstalk.

Main Methods:

  • Literature review of recent findings on DDR1, IR, and IGF-1R.
  • Analysis of molecular interactions and signaling pathways (PI3K/AKT/miR-199a-5p).
  • Discussion of DDR1's role in regulating cellular responses to external stimuli.

Main Results:

  • DDR1 interacts with IR and IGF-1R, enhancing the biological actions of insulin, IGF-1, and IGF-2.
  • DDR1 is upregulated by insulin, IGF-1, and IGF-2 via the PI3K/AKT/miR-199a-5p pathway.
  • DDR1 acts as a regulator of cellular responses to hormones, growth factors, and extracellular matrix signals.

Conclusions:

  • DDR1 is a novel modulator of IIGFs signaling in cancer.
  • The DDR1-IIGFs axis represents a potential therapeutic target for cancer treatment.
  • DDR1 plays a broader role in regulating cell responses to diverse signaling pathways.
Keywords:
breast cancerdiscoidin domain receptor 1insulin receptor isoform Ainsulin-like growth factor axisinsulin-like growth factor-2

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