scholarly journals Discoidin Domain Receptor 2 Interacts with Src and Shc following Its Activation by Type I Collagen

2002 ◽  
Vol 277 (21) ◽  
pp. 19206-19212 ◽  
Author(s):  
Kazuo Ikeda ◽  
Li-Hsien Wang ◽  
Richard Torres ◽  
Hong Zhao ◽  
Elvira Olaso ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2

scholarly journals Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression

Oncotarget ◽  
2016 ◽  
Vol 7 (18) ◽  
pp. 24908-24927 ◽  
Author(s):  
Charles Saby ◽  
Emilie Buache ◽  
Sylvie Brassart-Pasco ◽  
Hassan El Btaouri ◽  
Marie-Pierre Courageot ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Type I Collagen ◽  
Growth Suppression ◽  
Type I ◽  
Tumor Cell Growth ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2 ◽  
Cell Growth Suppression

scholarly journals Discoidin Domain Receptor 1 Protein Is a Novel Modulator of Megakaryocyte-Collagen Interactions

2013 ◽  
Vol 288 (23) ◽  
pp. 16738-16746 ◽  
Author(s):  
Vittorio Abbonante ◽  
Cristian Gruppi ◽  
Diana Rubel ◽  
Oliver Gross ◽  
Remigio Moratti ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Discoidin Domain Receptor ◽  
Glycoprotein Vi ◽  
Protein Levels ◽  
Collagen Receptors ◽  
And Function ◽  
Extracellular Matrix Receptors ◽  
Collagen Receptor ◽  
Discoidin Domain Receptor 1

Growing evidence demonstrates that extracellular matrices regulate many aspects of megakaryocyte (MK) development; however, among the different extracellular matrix receptors, integrin α2β1 and glycoprotein VI are the only collagen receptors studied in platelets and MKs. In this study, we demonstrate the expression of the novel collagen receptor discoidin domain receptor 1 (DDR1) by human MKs at both mRNA and protein levels and provide evidence of DDR1 involvement in the regulation of MK motility on type I collagen through a mechanism based on the activity of SHP1 phosphatase and spleen tyrosine kinase (Syk). Specifically, we demonstrated that inhibition of DDR1 binding to type I collagen, preserving the engagement of the other collagen receptors, glycoprotein VI, α2β1, and LAIR-1, determines a decrease in MK migration due to the reduction in SHP1 phosphatase activity and consequent increase in the phosphorylation level of its main substrate Syk. Consistently, inhibition of Syk activity restored MK migration on type I collagen. In conclusion, we report the expression and function of a novel collagen receptor on human MKs, and we point out that an increasing level of complexity is necessary to better understand MK-collagen interactions in the bone marrow environment.

scholarly journals Collagen and Discoidin Domain Receptor 1 Partnership: A Multifaceted Role in the Regulation of Breast Carcinoma Cell Phenotype

2021 ◽  
Vol 9 ◽  
Author(s):  
Charles Saby ◽  
Erik Maquoi ◽  
Frédéric Saltel ◽  
Hamid Morjani
Keyword(s):  
Cell Proliferation ◽  
Breast Carcinoma ◽  
Type I Collagen ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Type I ◽  
Collagen Remodeling ◽  
Breast Carcinoma Cells ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 1

Type I collagen, the major components of breast interstitial stroma, is able to regulate breast carcinoma cell behavior. Discoidin domain receptor 1 (DDR1) is a type I collagen receptor playing a key role in this process. In fact, collagen/DDR1 axis is able to trigger the downregulation of cell proliferation and the activation of BIK-mediated apoptosis pathway. The aim of this review is to discuss the role of two important factors that regulate these processes. The first factor is the level of DDR1 expression. DDR1 is highly expressed in epithelial-like breast carcinoma cells, but poorly in basal-like ones. Moreover, DDR1 undergoes cleavage by MT1-MMP, which is highly expressed in basal-like breast carcinoma cells. The second factor is type I collagen remodeling since DDR1 activation depends on its fibrillar organization. Collagen remodeling is involved in the regulation of cell proliferation and apoptosis through age- and proteolysis-related modifications.

DDR2 induces linear invadosome to promote angiogenesis in a fibrillar type I collagen context

2020 ◽  
Author(s):  
Aya Abou Hammoud ◽  
Sébastien Marais ◽  
Nathalie Allain ◽  
Zakaria Ezzoukhry ◽  
Violaine Moreau ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Ex Vivo ◽  
Type I ◽  
Matrix Degradation ◽  
The Matrix ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor

AbstractTo generate new vessels, endothelial cells (ECs) form invadosomes, which are actin-based microdomains with a proteolytic activity that degrade the basement membrane. We previously demonstrated that ECs form linear invadosomes in fibrillar type I collagen context. In this study, we aim to investigate the molecular mechanisms by which ECs guides angiogenesis in a fibrillar type I collagen context. We found that Discoidin Domain Receptor 2 (DDR2) is the collagen receptor tyrosine kinase required to form linear invadosomes in ECs. We further demonstrated that it acts in synergy with VEGF to promote extracellular matrix degradation. We highlighted the involvement of an interaction between DDR2 and the matrix metalloproteinase MMP14 in this process. Finally, using in vitro and ex-vivo angiogenesis assays, we demonstrated a pro-angiogenic function of DDR2 in a collagen-rich microenvironment. This study allows us to propose DDR2-dependent linear invadosomes as targets to modulate angiogenesis.

scholarly journals Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42–Tuba pathway

2014 ◽  
Vol 207 (4) ◽  
pp. 517-533 ◽  
Author(s):  
Amélie Juin ◽  
Julie Di Martino ◽  
Birgit Leitinger ◽  
Elodie Henriet ◽  
Anne-Sophie Gary ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Type I Collagen ◽  
Type I ◽  
Dependent Manner ◽  
Nucleotide Exchange ◽  
Independent Manner ◽  
Src Tyrosine Kinase ◽  
Discoidin Domain Receptor ◽  
Increased Risk ◽  
Discoidin Domain Receptor 1

Accumulation of type I collagen fibrils in tumors is associated with an increased risk of metastasis. Invadosomes are F-actin structures able to degrade the extracellular matrix. We previously found that collagen I fibrils induced the formation of peculiar linear invadosomes in an unexpected integrin-independent manner. Here, we show that Discoidin Domain Receptor 1 (DDR1), a collagen receptor overexpressed in cancer, colocalizes with linear invadosomes in tumor cells and is required for their formation and matrix degradation ability. Unexpectedly, DDR1 kinase activity is not required for invadosome formation or activity, nor is Src tyrosine kinase. We show that the RhoGTPase Cdc42 is activated on collagen in a DDR1-dependent manner. Cdc42 and its specific guanine nucleotide-exchange factor (GEF), Tuba, localize to linear invadosomes, and both are required for linear invadosome formation. Finally, DDR1 depletion blocked cell invasion in a collagen gel. Altogether, our data uncover an important role for DDR1, acting through Tuba and Cdc42, in proteolysis-based cell invasion in a collagen-rich environment.

Sign in / Sign up

Export Citation Format

Share Document