Extracellular matrix (ECM) provides cells scaffolding for cell migration and microenvironment for various cellular functions. Collagens are major ECM components in tissue and discoidin domain receptors (DDRs) are receptor tyrosine kinases (RTK) that recognise fibrillar collagens. Unlike other RTK, their ligands are solid ECM the that are abundantly present in the pericellular environment in various tissue, and thus its activation and regulations are unique amongst RTK family. It is emerging that DDRs may be the sensors that monitor and detects changes in ECM microenvironment and determines the cellular fates upon tissue injuries. In this mini-review, recent findings on the role of DDRs as microenvironment sensor and their roles in cell migration and invasion are discussed.
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http://dx.doi.org/10.1080/19336918.2018.1460011 | DOI Listing |
JBMR Plus
February 2025
Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, United States.
Discoidin Domain Receptor 1 (DDR1) is a receptor tyrosine kinase that binds to and is activated by collagen(s), including collagen type I. deletion in osteoblasts and chondrocytes has previously demonstrated the importance of this receptor in bone development. In this study, we examined the effect of DDR1 ablation on bone architecture and mechanics as a function of aging.
View Article and Find Full Text PDFMolecules
December 2024
Grup de Química Farmacèutica, IQS School of Engineering, Universitat Ramon Llull, Via Augusta 390, E-08017 Barcelona, Spain.
In cases in which a rapid metabolism is the cause of an unfavorable pharmacokinetic profile, it is important to determine the Sites of Metabolism (SoMs) of a molecule to introduce the necessary modifications to improve the stability of the compound. The substitution of hydrogen atoms by deuterium atoms has been proposed to ameliorate such properties due to the greater stability of the C-D bonds. , bearing a 2-phenylamino substituent, is a compound previously described by our group with good biological activity as a discoidin domain receptor (DDR2) inhibitor but suffers from low metabolic stability determined in a test with rat-liver microsomes (less than 50% of the initial compound after 60 min).
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
: Chemoresistance is an important issue to be solved in breast cancer. It is well known that the content and morphology of collagens in tumor tissues are drastically altered following chemotherapy, and discoidin domain receptor 2 (DDR2) is a unique type of receptor tyrosine kinase (RTK). This RTK is activated by collagens, playing important roles in human malignancies.
View Article and Find Full Text PDFBone Res
January 2025
Department of Periodontics & Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification (HO). Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO. This study focuses on the ability of the collagen receptor, discoidin domain receptor 2 (DDR2), to regulate BMP activity.
View Article and Find Full Text PDFInvest New Drugs
December 2024
Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Melanoma, one of the most prevalent cancers worldwide, frequently metastasizes to the lung and bones. Tumor-associated macrophages play essential roles in melanoma metastasis but the underlying mechanism remains obscure. We previously demonstrated that specific knockout of Ddr2, a receptor tyrosine kinase, exacerbates systemic inflammation via modulating macrophage repolarization.
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