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:6/3/2016)... , June 3, 2016 ... von Nepal hat ... Lieferung hochsicherer geprägter Kennzeichen, einschließlich Personalisierung, Registrierung ... in der Produktion und Implementierung von Identitätsmanagementlösungen. ... Ausschreibung im Januar teilgenommen, aber Decatur wurde ...
(Date:6/2/2016)... -- Perimeter Surveillance & Detection Systems, Biometrics ... Support & Other Service  The latest report ... analysis of the global Border Security market . ... $17.98 billion in 2016. Now: In November ... software and hardware technologies for advanced video surveillance. ...
(Date:5/20/2016)... -- VoiceIt is excited to announce its new marketing ... working together, VoiceIt and VoicePass will offer an ... slightly different approaches to voice biometrics, collaboration between ... Both companies ... "This marketing and technology partnership allows VoiceIt ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... BEACH, Calif. , June 23, 2016  Blueprint ... new biological discoveries to the medical community, has closed ... co-founder Matthew Nunez . "We have ... us with the capital we need to meet our ... will essentially provide us the runway to complete validation ...
(Date:6/23/2016)... On Wednesday, June 22, 2016, the ... the Dow Jones Industrial Average edged 0.27% lower to finish ... 0.17%. Stock-Callers.com has initiated coverage on the following equities: Infinity ... NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ... ). Learn more about these stocks by accessing their free ...
(Date:6/23/2016)... ... 23, 2016 , ... Regulatory Compliance Associates® Inc. (RCA), a ... webinar on Performing Quality Investigations: Getting to Root Cause. This ... charge. , Incomplete investigations are still a major concern to the Regulatory Authorities ...
(Date:6/23/2016)... June 22, 2016  Amgen (NASDAQ: AMGN ... QB3@953 life sciences incubator to accelerate the ... shared laboratory space at QB3@953 was created to help ... obstacle for many early stage organizations - access to ... sponsorship, Amgen launched two "Amgen Golden Ticket" awards, providing ...
Breaking Biology Technology: