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Review
. 2018;12(4):315-323.
doi: 10.1080/19336918.2018.1520556. Epub 2018 Oct 13.

Signaling by discoidin domain receptor 1 in cancer metastasis

Mayur Gadiya  1   2 , Goutam Chakraborty  3
Affiliations
Review

Signaling by discoidin domain receptor 1 in cancer metastasis

Mayur Gadiya et al. Cell Adh Migr. 2018.

Abstract

Collagen is the most abundant component of tumor extracellular matrix (ECM). ECM collagens are known to directly interact with the tumor cells via cell surface receptor and play crucial role in tumor cell survival and promote tumor progression. Collagen receptor DDR1 is a member of receptor tyrosine kinase (RTK) family with a unique motif in the extracellular domain resembling Dictyostelium discoideum protein discoidin-I. DDR1 displays delayed and sustained activation upon interaction with collagen and recent findings have demonstrated that DDR1-collagen signaling play important role in cancer progression. In this review, we discuss the current knowledge on the role of DDR1 in cancer metastasis and possibility of a potential therapeutic approach of DDR1 targeted therapy in cancer.

Keywords: Cell Signaling; DDR1; Dormancy; Metastasis; TM4SF1.

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Figures

Figure 1.
Figure 1.
(a & b) DDR1 and DDR2 mRNA expression in human tissue analyzed by GTEx portal (www.gtexportal.org). (c) Distribution of DDR1 and DDR2 expressions in benign human tissue analyzed by human proteome map (http://www.humanproteomemap.org/).
Figure 2.
Figure 2.
Pan cancer analysis of DDR1 alteration (Amplification, Mutation & deep Deletion).
Figure 3.
Figure 3.
(a) Schematic Representation of DDR1-collagen signaling pathway in cancer. Collagen DDR1 interaction induces canonical and non-canonical signaling pathway which is summarize in the figure. Canonically interaction between collagen and DDR1 induces tyrosine phosphorylation of DDR1 and induces DDR1 kinase activation. DDR1 kinase activation induces Src, Notch and IKK signaling pathway. DDR1 also regulates Pyk2 mediate RAP1 activation that leads to epithelial to mesenchymal transition (EMT). Collagen also induces DDR1 and TM4SF1 interaction which is a kinase independent (Non-canonical; inside box) function of DDR1. DDR1-TM4SF1 interaction regulates survival and reactivation of breast cancer cells in metastatic site [3].(b) Schematic Representation of DDR1-collagen signaling on induction/activation of MMP that regulates degradation of matrix and invasiveness of cancer cells.
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