Asian Scientist (Jul. 25, 2013) – Researchers have uncovered new details about the biological network that instructs cells to propel themselves in a particular direction.
The discovery may lead to new strategies for stopping the migration of tumor cells and thereby preventing metastasis in cancer patients.
In their study, published in Molecular Biology of the Cell, the researchers studied the mechanism by which fibroblasts migrate from one site to another.
Fibroblasts are the most common cells that form connective tissue in animals. When healthy tissues sustain an injury, fibroblasts move into the area to repair the damage.
Although the key components of the cell migration signaling network were already known, it was uncertain how they are interconnected and how signals to migration are passed from one component to another.
To uncover the details of this network, the researchers focused on two important network components, known as Ras and PI3K.
Although Ras is known to activate PI3K, passing on the migration signal in a linear manner, the researchers suspected that there may be other interactions going on between Ras and PI3K.
Using an approach that allowed activation of PI3K without going through Ras, the researchers revealed the existence of a positive feedback loop between PI3K and HRas (one of three Ras proteins implicated in cancer): activation of PI3K by Ras proteins (including HRas) results in feedback activation of HRas by PI3K.
This positive feedback loop results in a self-perpetuating signal that is switched on in very specific regions in fibroblast cells. The signal causes proteins to push against one side of the cell, causing movement in one preferred direction.
Because Ras and PI3K proteins are often mutated in cancer, abnormal activation of this network may increase the tendency of cancer cells to spread.
Therefore, the researchers hope that targeting this self-perpetuating signal in cancer cells may help in preventing cancer metastasis.
The article can be found at: Thevathasan et al. (2013) The Small GTPase HRas Shapes Local PI3K Signals Through Positive Feedback And Regulates Persistent Membrane Extension In Migrating Fibroblasts.
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Copyright: Asian Scientist Magazine; Photo: Tom Anderson/Flickr.
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