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New understanding of cell movement may yield ways to brake cancer's spread

ule called DOCK180, a key signaling protein that binds to PIP3. PIP3 is a lipid that accumulates on the leading edge of a cell about to move, usually in response to a number of outside cellular attractants like chemokines, growth factors and other molecules. Meanwhile at the hind end of the cell, enzymes degrade the PIP3 lipid, creating a gradient from one end of the cell to the other.

It is this PIP3 lipid gradient that sets the cell into motion toward the right direction. The PIP3-binding portion of DOCK180 senses the gradient, and DOCK180 starts accumulating at the leading edge of the cell. Along with it, DOCK180 brings a host of additional molecules to the leading edge, triggering a series of internal events that begin moving the cell forward. "We see a protrusion form first, in which the cell changes shape and extends towards the direction it is about to go, followed by movement of the rest of the cell," Vuori said.

Now, the researchers are looking at developing a three-dimensional picture of PIP3 -binding domain's molecular structure. "We are currently planning these structure studies with our collaborators here at the Burnham," Vuori said. "If we know its molecular structure, we hope to be able to make small chemicals that inhibit inappropriate cell migration, including the types seen in metastatic cancer cells."


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Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-646-3146
Burnham Institute
29-Jul-2005


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