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.

A comparison of spreading and motility behaviour of 8701-BC breast carcinoma cells on type I, I-trimer and type V collagen substrata. Evidence for a permissive effect of type I-trimer collagen on cell locomotion

1991 ◽  
Vol 100 (1) ◽  
pp. 179-185
Author(s):  
C. Luparello ◽  
P. Sheterline ◽  
I. Pucci-Minafra ◽  
S. Minafra
Keyword(s):  
Breast Carcinoma ◽  
Type I Collagen ◽  
Tumour Cells ◽  
Host Tissue ◽  
Carcinoma Cells ◽  
Type I ◽  
Rhodamine Phalloidin ◽  
Type V Collagen ◽  
Breast Carcinoma Cells ◽  
Type V

Ductal infiltrating carcinoma (d.i.c.) of human breast is a highly invasive neoplasm characterized by enhanced deposition of collagen. Paradoxically, enhanced collagen deposition is not correlated with inhibition of the migration of tumour cells into the host tissue. d.i.c. is characterized by the reappearance of ‘embryonic’ type I-trimer collagen and an increase in type V collagen content in the matrix. The effects of these two collagen types were compared with type I collagen as culture substrata on the spreading pattern, cytoskeletal organization and motile behaviour of 8701-BC breast carcinoma cells using rhodamine-phalloidin staining, a DNAase I-competition assay, scanning electron microscopy and time-lapse video-microscopy. Cells grown on type I collagen were stationary, showing a well-spread morphology and an extensive stress fibre pattern. Cells grown on type V collagen were also stationary, but displayed a poorly spread and elongated morphology. In contrast, cells grown on trimer collagen were motile and displayed a compact morphology and a reduced content of stress fibres. Both single-cell and group motility were detectable on trimer collagen substratum. These data are consistent with the existence of two opposite local signals, type I-trimer and type V collagens, which may confer a more or a less metastatic phenotype on breast carcinoma cells. Moreover, the synthesis of trimer collagen in d.i.c. is conceivably instrumental in providing new stromal pathways permitting tumour cells to infiltrate the host tissue.

scholarly journals MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis

Oncogene ◽  
2011 ◽  
Vol 31 (4) ◽  
pp. 480-493 ◽  
Author(s):  
E Maquoi ◽  
D Assent ◽  
J Detilleux ◽  
C Pequeux ◽  
J-M Foidart ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Type I Collagen ◽  
Carcinoma Cells ◽  
Type I ◽  
Breast Carcinoma Cells ◽  
Induced Apoptosis

scholarly journals Site-Directed Perturbation of Protein Kinase C- Integrin Interaction Blocks Carcinoma Cell Chemotaxis

2002 ◽  
Vol 22 (16) ◽  
pp. 5897-5911 ◽  
Author(s):  
Maddy Parsons ◽  
Melanie D. Keppler ◽  
Adam Kline ◽  
Anthea Messent ◽  
Martin J. Humphries ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Breast Carcinoma ◽  
Tumor Cell ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Cell Phenotype ◽  
Β1 Integrin ◽  
Breast Carcinoma Cells ◽  
Tumor Cell Motility ◽  
Cell Chemotaxis

ABSTRACT Polarized cell movement is an essential requisite for cancer metastasis; thus, interference with the tumor cell motility machinery would significantly modify its metastatic behavior. Protein kinase Cα (PKCα) has been implicated in the promotion of a migratory cell phenotype. We report that the phorbol ester-induced cell polarization and directional motility in breast carcinoma cells is determined by a 12-amino-acid motif (amino acids 313 to 325) within the PKCα V3 hinge domain. This motif is also required for a direct association between PKCα and β1 integrin. Efficient binding of β1 integrin to PKCα requires the presence of both NPXY motifs (Cyto-2 and Cyto-3) in the integrin distal cytoplasmic domains. A cell-permeant inhibitor based on the PKC-binding sequence of β1 integrin was shown to block both PKCα-driven and epidermal growth factor (EGF)-induced chemotaxis. When introduced as a minigene by retroviral transduction into human breast carcinoma cells, this inhibitor caused a striking reduction in chemotaxis towards an EGF gradient. Taken together, these findings identify a direct link between PKCα and β1 integrin that is critical for directed tumor cell migration. Importantly, our findings outline a new concept as to how carcinoma cell chemotaxis is enhanced and provide a conceptual basis for interfering with tumor cell dissemination.

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.

KV1.1 K+ Channels Identification in Human Breast Carcinoma Cells: Involvement in Cell Proliferation

2000 ◽  
Vol 278 (2) ◽  
pp. 272-277 ◽  
Author(s):  
H. Ouadid-Ahidouch ◽  
F. Chaussade ◽  
M. Roudbaraki ◽  
C. Slomianny ◽  
E. Dewailly ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Breast Carcinoma ◽  
Carcinoma Cells ◽  
Human Breast Carcinoma ◽  
Human Breast ◽  
K Channels ◽  
Breast Carcinoma Cells ◽  
Human Breast Carcinoma Cells

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.

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