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Metastatic movements in 3-D
October 06, 2008Caswell et al.report in the Journal of Cell Biology how the altered behavior of integrins can prompt metastatic movement in tumor cells.
On 2D surfaces, cells may migrate randomly, or be strongly unidirectional. Integrins, which link the cell to the extracellular matrix, are known to influence the mode of migration, but exactly how has been unclear. Recent work has suggested that an integrin called a5b1 drives random movement, while an integrin called avb3 has been associated with unidirectional migration-the balance of activity between the two determining the type of movement. To further explore the contribution of a5b1 to random migration, the authors thus blocked avb3.
The treated cells changed their mode of migration from unidirectional to random, and their ability to invade 3D gels increased. The changed behavior correlated with an increase in trafficking of a5b1 from intracellular compartments to anterior membrane protrusions. But this increase in trafficking did not significantly alter a5b1's contribution to cell adhesion-the ease with which cells were dislodged from a spinning disk increased as the amount of avb3 was reduced, but was not correlated with any change in a5b1. This suggested that the cells' increased invasive ability was due to alteration in some other property. That property turned out to be activation of a proinvasive pathway headed by a kinase called Akt.
In avb3-blocked cells, a5b1 became associated with epidermal growth factor receptor 1 (EGFR1), which increased EGFR1's abundance at the membrane protrusions, as well as its autophosphorylation. Because EGFR1 is an activator of the Akt pathway, hey presto, the cells took on some new moves.
Rockefeller University Press
In avb3-blocked cells, a5b1 became associated with epidermal growth factor receptor 1 (EGFR1), which increased EGFR1's abundance at the membrane protrusions, as well as its autophosphorylation. Because EGFR1 is an activator of the Akt pathway, hey presto, the cells took on some new moves.
Rockefeller University Press
Integrins Current Events and Integrins News RSSResearchers coat titanium with polymer to improve integration of joint replacements
Research at the Georgia Institute of Technology shows that coating a titanium implant with a new biologically inspired material enhances tissue healing, improves bone growth around the implant and strengthens the attachment and integration of the implant to the bone.
Integrins as receptors give insight into rotavirus and diarrhea
Eleven years ago, Dr. Mary Estes of Baylor College of Medicine and her colleagues discovered the first viral enterotoxin, rotavirus NSP4, a toxic protein that affects the intestines, causing diarrhea.
Cell surface receptors are all 'talk' in T cell stimulation
Understanding the mechanisms that drive healthy immune responses is important when it comes to combating autoimmune diseases, which occur when cells that should attack invading organisms turn on the body instead.
Researchers find new way to block destructive rush of immune cells
Researchers have found a way to selectively block the ability of white blood cells to "crawl" toward the sites of injury and infection when such mobility drives disease, according to a study published today in The Journal of Experimental Medicine.
UCSD researchers create roadmap to integrin activation
Calling it an important technical advance in the study of the complex receptors and pathways of the body's cellular system, researchers at the University of California, San Diego (UCSD) School of Medicine have reconstructed the signaling pathways that impact activation of a receptor that is critical to the control of bleeding and to the thrombosis that occurs in heart attacks and strokes.
Researchers reveal lung's unique innate immune system
For the first time, scientists have documented an organ-specific innate immune system. In research published in the April 18 edition of the journal Immunity, scientists at the University of California, San Diego (UCSD) School of Medicine outline the unique mechanism by which the lung shapes its defensive strategies against microbial invasion.
Preventing toxic side effects of inflammatory disease therapy
Researchers at the University of California, San Diego (UCSD) School of Medicine have developed a mouse model that could help scientists develop better drugs to fight autoimmune and inflammatory disorders such as multiple sclerosis and rheumatoid arthritis.
Loss of caspase-8 makes neuroblastoma more aggressive
The caspase-8 gene plays a critical role in suppressing metastasis (spread) of neuroblastoma, and the expression of this gene is frequently absent in cancer cells that are aggressively metastasizing.
Cancer researchers describe gene that halts spread of aggressive childhood cancer
A team of cancer researchers has shown that a gene commonly lost during neuroblastoma tumor formation, one of the most aggressive cancers in babies and children, is in fact a "metastasis suppressor" gene.
Tissue stiffness drives tumor formation
The relationship between tissue rigidity and tumor formation is fairly well established; however, what is not so well understood is what happens on a molecular level that contributes to such stiffness.
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| Domain I Integrins | |
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| Integrins and Icam-1 in Immune Responses (Chemical Immunology) (v. 50) by Nancy Hogg | |
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