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Books > Science & Mathematics > Biology, life sciences > Cellular biology
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Discoidin Domain Receptors in Health and Disease (Hardcover, 1st ed. 2016)
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Discoidin Domain Receptors in Health and Disease (Hardcover, 1st ed. 2016)
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The interactions of cells with their surrounding extracellular
matrix (ECM) plays a pivotal role in driving normal cell behavior,
from development to tissue differentiation and function. At the
cellular level, organ homeostasis depends on a productive
communication between cells and ECM, which eventually leads to the
normal phenotypic repertoire that characterize each cell type in
the organism. A failure to establish these normal interactions and
to interpret the cues emanating from the ECM is one of the major
causes in abnormal development and the pathogenesis of multiple
diseases. To recognize and act upon the biophysical signals that
are generated by the cross talk between cells and ECM, the cells
developed specific receptors, among them a unique set of receptor
tyrosine kinases (RTKs), known as the Discoidin Domain Receptors
(DDRs). The DDRs are the only RTKs that specifically bind to and
are activated by collagen, a major protein component of the ECM.
Hence, the DDRs are part of the signaling networks that translate
information from the ECM, and thus they are key regulators of
cell-matrix interactions. Under physiological conditions, DDRs
control cell and tissue homeostasis by acting on collagen sensors;
transducing signals that regulate cell polarity, tissue
morphogenesis, cell differentiation, and collagen deposition. DDRs
play a key role in diseases that are characterized by dysfunction
of the stromal component, which lead to abnormal collagen
deposition and the resulting fibrotic response that disrupt normal
organ function in disease of the cardiovascular system, lungs and
kidneys, just to mention a few. In cancer, DDRs are hijacked by
tumor and stromal cells to disrupt normal cell-collagen
communication and initiate pro-oncogenic programs. Importantly,
several cancer types exhibit DDR mutations, which are thought to
alter receptor function, and contribute to cancer progression.
Therefore, the strong causative association between altered RTK
function and disease it is been translated today in the development
of specific tyrosine kinase inhibitors targeting DDRs for various
disease conditions. In spite of the accumulating evidence
highlighting the importance of DDRs in health and diseases, there
is still much to learn about these unique RTKs, as of today there
is a lack in the medical literature of a book dedicated solely to
DDRs. This is the first comprehensive volume dedicated to DDRs,
which will fill a gap in the field and serve those interested in
the scientific community to learn more about these important
receptors in health and disease.
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