Navigation Links
Protein key to cell motility has implications for stopping cancer metastasis
Date:3/12/2014

PHILADELPHIA - "Cell movement is the basic recipe of life, and all cells have the capacity to move," says Roberto Dominguez, PhD, professor of Physiology at the Perelman School of Medicine, University of Pennsylvania. Motility albeit on a cellular spatial scale -- is necessary for wound healing, clotting, fetal development, nerve connections, and the immune response, among other functions. On the other hand, cell movement can be deleterious when cancer cells break away from tumors and migrate to set up shop in other tissues during cancer metastasis.

The Dominguez team, with postdoctoral fellow David Kast, PhD, and colleagues, report online ahead of print in Nature Structural & Molecular Biology how a key cell-movement protein called IRSp53 is regulated in a resting and active state, and what this means for cancer-cell metastasis.

"We characterized how IRSp53 connects to the cell-motility machinery," says Kast. "It does this by starting the formation of cell filopodia - extensions that form when a cell needs to move."

"Cells move like an inchworm," explains Dominguez. "Filopodia are at the leading edge of moving cells." The trailing end of the cell follows the move forward through contraction of actin and myosin in the cytoskeleton, much like muscle contraction. A cell pushes out the leading edge of its membrane, and sticks it down on whatever it is moving across, namely other cells, and then moves the cell body along, unsticking the back end. This sets the cell up for its next move.

IRSp53 contains a region called a BAR domain that binds to and shapes cell membranes. Other parts of the protein connect it to the cytoskeleton (internal bits that give a cell structure and shape). Together, through the binding of cell membranes and other proteins IRSp53 regulates cell movement. The team found that in the resting state, human IRSp53 adopts a closed shape that prevents it from interacting with the membrane and the cytoskeleton. However, the binding of a signaling protein, called Cdc42, opens IRSp53, setting in motion the recruitment of a complex cellular machinery needed for motility.

One of the cytoskeleton components IRSp53 connects to is the tumor-promoting protein Eps8. IRSp53 is synergistically activated by the combined action of Cdc42 and binding of Eps8, which is upregulated in metastatic cancers.

Co-authors Tatyana Svitkina and Changsong Yang from the Penn Department of Biology, brought their expertise with living cells to the study. By introducing normal and mutant proteins into cells they could see how these proteins induced filopodia to form. The team found that mutations in critical regions of IRSp53 can either lead to enhanced or reduced filopodia formation and, as a consequence, cell motility. "This finding shows how all these different proteins converge on IRSp53 to execute precise cellular functions, and that when one factor is disrupted, other proteins are affected down the activity pathway," says Dominguez.

The team's next steps will be to screen libraries of small molecule inhibitors that interfere with the IRSp53-Eps8 interaction, to figure out how to stop unwanted cell movement before it gets too far.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related biology news :

1. Fruit flies help uncover tumor-preventing protein complex
2. Diets high in animal protein may help prevent functional decline in elderly individuals
3. Phosphorylation of tau protein in rats subjected to cerebral ischemia-reperfusion injury
4. New probes from Scripps research quantify folded and misfolded protein levels in cells
5. Characterization of stink bug saliva proteins opens door to controlling pests
6. A key protein is discovered as essential for malaria parasite transmission to mosquitos
7. A*STAR scientists discover proteins role in human memory and learning functions
8. Mitosis mystery solved as role of key protein is confirmed
9. Superbright and fast X-rays image single layer of proteins
10. New insight into protein misfolding in neurodegenerative disorders
11. A role of glucose tolerance could make the adaptor protein p66Shc a new target for cancer and diabetes
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Protein key to cell motility has implications for stopping cancer metastasis
(Date:4/4/2017)...   EyeLock LLC , a leader of iris-based ... Patent and Trademark Office (USPTO) has issued U.S. Patent ... an iris image with a face image acquired in ... 45 th issued patent. "The ... the multi-modal biometric capabilities that have recently come to ...
(Date:3/29/2017)... 2017  higi, the health IT company that operates ... America , today announced a Series B investment ... EveryMove. The new investment and acquisition accelerates higi,s strategy ... transform population health activities through the collection and workflow ... higi collects and secures data today on behalf of ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by ... Global Forecast to 2022", published by MarketsandMarkets, the market is expected to be ... 2017 and 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:5/23/2017)... ... May 23, 2017 , ... Genedata, a leading ... marking the occasion with a strong presence at Bio-IT World Conference & Expo ... extends an invitation to all attendees to view posters on the entire ...
(Date:5/23/2017)... ... May 22, 2017 , ... ... 2017 in San Diego, California, this August will feature high-level speakers on ... autonomous vehicles. , SPIE Optics and Photonics, the largest multidisciplinary optical sciences meeting ...
(Date:5/23/2017)... , ... May 23, 2017 , ... ... advanced technology applications, has announced a facility expansion to accommodate its rapid growth. ... feet of new workspace and renovation of the existing areas. The expansion includes, ...
(Date:5/23/2017)... , ... May 23, 2017 , ... Bacterial biofilms, surface ... molecules, can cause diverse pathologies ranging from food poisoning and catheter infections to gum ... is in the tens of billions of dollars per year, there is currently a ...
Breaking Biology Technology: