Navigation Links
New clue to controlling skin regeneration -- as well as skin cancer
Date:3/3/2011

How do organs "know" when to stop growing? The answer could be useful in regenerative medicine, and also in cancer where these "stop growing" signals either aren't issued or aren't heeded. Researchers in the Stem Cell Program at Children's Hospital Boston have now found a regulator of gene activity that tells epidermal stem cells when it's time to grow more skin, as well as a "crowd control" molecule that can sense cell crowding and turn the growth off.

The work, in mice and in human cancer cells, provides clues to new therapeutic strategies for cancer, particularly squamous cell carcinoma, the second most common skin cancer, in which epidermal cell growth is inappropriately turned on. It could also aid efforts to grow skin grafts and treat burn patients.

The findings, published in Cell on March 4, underscore the idea that cancer and regeneration are closely related. "We have found a molecular switch that tells your skin to keep growing or stop growing," says Fernando Camargo, PhD, the study's senior investigator and a principal investigator in Children's Stem Cell Program.

Camargo and colleagues manipulated a molecule called Yap1, already known from studies in fruit flies to cause massive tumor growth by triggering a pathway known as Hippo (so named because of the enormous size of the tumors). When they suppressed Yap1 function in mice, their epidermal skin stem cells failed to expand and they had thin, fragile skin.

The opposite was also true. "The more Yap1 you have in your stem cells, the thicker your skin grows," says Camargo, who is also a member of the Harvard Stem Cell Institute.

However, activation of Yap1 also caused the mice to develop squamous-cell carcinoma-like tumors, the researchers found.

They further showed that Yap1 is inactivated by a known tumor suppressor called alpha-catenin, which binds to Yap1 and keeps it outside the cell nucleus. In both mice and human squamous carcinoma cells with alpha-catenin mutations, Yap1 returns to the nucleus and becomes active again.

"Alpha catenin is silenced in many types of epithelial cancer skin cancer, colon cancer and other squamous cell cancers," says Camargo. "When alpha catenin is absent or mutated, you get an overgrowth of cells, but until now it was unclear why. Our work suggests that over-activation of Yap 1 is likely what drives these cancers."

Alpha-catenin is known to be able to sense the density of cells in its immediate environment, and perhaps even their type. Camargo's team revealed how the information is used: When cells are packed too tightly, alpha-catenin inhibits Yap1 the first demonstration of a direct link between an environmental cue (cell density) and a molecular regulator of organ size. Until now, little has been known about what maintains organs at a specific size.

"Through Yap1, alpha-catenin tells epidermal stem cells to either proliferate or not proliferate, depending on the needs of the tissue," Camargo explains.

Now that the "switch" for skin growth is known, manipulating it could provide ways to grow skin cells when they're needed or, conversely, to stop cancerous growth. Camargo's group is conducting screening tests to find small molecules that mimic Yap1, to induce skin regeneration at the site of a wound, or that inhibit Yap1 to treat skin tumors. The team is also looking for other molecules that may also interact with Yap1.


'/>"/>

Contact: Colleen Connolly
Colleen.Connolly@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

Related medicine news :

1. Controlling the rising costs of cardiovascular care
2. Controlling symptoms can lead to improved quality of life for end-of-life patients
3. Health Secretary Encourages Pennsylvanians to Learn the ABCs of Controlling Diabetes
4. UCSD receives NIH Transformative R01 Award for stimulation of neuron regeneration in the retina
5. Scientists Discover Molecular Pathway for Organ Tissue Regeneration and Repair
6. Student innovation at Rensselaer Polytechnic Institute could lead to better breast cancer screening
7. Researchers pinpoint genetic pathways involved in breast cancer
8. Cancer patients partners become ill themselves
9. Australia Fellowship gives $4 million boost to cancer origin research
10. New Chemo Drug May Benefit Some Breast Cancer Patients
11. Penn researchers find new role for cancer protein p53
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/8/2016)... ... December 08, 2016 , ... ... development continuity to its innovative Unified Instance Manager architecture, meeting the needs ... this new version optimizes the unattended auto-dialing system without agents, Presence Robodialer, ...
(Date:12/8/2016)... ... December 08, 2016 , ... STAT courier is pleased to announce that ... for Texas, they are expanding their presence in Dallas. One of the most exciting ... bring new jobs to the Dallas and Forth Worth market. STAT takes pride in ...
(Date:12/8/2016)... ... December 08, 2016 , ... Healthcare is in flux. The ... for the mass media launching of story movements to highlight what's most unfair ... unfortunate experiences; such a movement can generate the network power to improve healthcare ...
(Date:12/8/2016)... (PRWEB) , ... December 08, 2016 , ... ... and financial planning services from offices headquartered in Hamilton County, is embarking on ... LuvFurMutts. , LuvFurMutts specializes in finding new homes for orphaned or neglected senior ...
(Date:12/8/2016)... , ... December 08, 2016 , ... Coppin Insurance Agency, ... and families in and around the Cape Coral area, is embarking on a charity ... Bank of Southwest Florida. , The Harry Chapin Food Bank of Southwest Florida works ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... Texas , Dec. 8, 2016 ... program that brings leading-edge laboratory services and management ... United States , allowing more doctors and ... health care management solutions. Logo - ... Hospital systems, under pressure to contain ...
(Date:12/8/2016)... 8, 2016 Information products and services provider ... in Scopus , the world,s largest abstract and citation database ... metrics for journals from over 5,000 publishers. The new set of ... subscribe to and when to adjust a journal,s editorial strategy. ... , , ...
(Date:12/8/2016)... A Small Business Innovative Research (SBIR) grant has been ... Phoenix -based NeuroEM Therapeutics, Inc. and ... seek to determine an optimal set of treatment parameters ... treat Alzheimer,s Disease. The grant will also investigate the ... neurologic disorders such as Parkinson,s Disease and PTSD. ...
Breaking Medicine Technology: