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:6/23/2017)... (PRWEB) , ... June 23, 2017 , ... Ulster University, ... June, 2017 from 9 am to 3 pm to present to graduate students exciting ... is an original curriculum project led by The Health Improvement Service of the ...
(Date:6/23/2017)... ... June 23, 2017 , ... ... financial planning services to communities in the greater Chicago metropolitan area, is embarking ... assistance to underprivileged youth in Chicago. , Founded in 1897, Hephzibah Children’s Association ...
(Date:6/23/2017)... ... June 23, 2017 , ... Radabaugh ... planning to families and business owners in North Central West Virginia, is embarking ... services to differently abled residents in the region. , The Stepping Stones organization ...
(Date:6/22/2017)... ... 2017 , ... Branches, Inc. has been partnering with The Miami Foundation for ... its programs focused on providing opportunity to low-income families and breaking the cycle of ... of $15,000 to support its , Climb to College & Career initiative which focuses ...
(Date:6/22/2017)... (PRWEB) , ... June 22, 2017 , ... ... advisory organization, is pleased to welcome Whipple & Company as its newest Partner ... clear purpose of balancing their clients’ risk while tailoring optimized benefit packages that ...
Breaking Medicine News(10 mins):
(Date:6/16/2017)... June 16, 2017 Datascope Corp. is voluntarily performing a worldwide ... a potential electrical test failure code.     ... PART NUMBER ... CS300 IABP 0998-UC-0446HXX; 0998-UC-0479HXX ... This field correction ...
(Date:6/13/2017)... , June 13, 2017 Zimmer Biomet Holdings, ... healthcare, today announced that the U.S. Food and Drug Administration ... June 3, 2015 relating to its Zhejiang, China ... "The successful clearance of the Warning ... manufacturing facility is a measure of the progress we ...
(Date:6/9/2017)... INDIANAPOLIS , June 9, 2017 ... In a further effort to help spread lessons learned ... condition, the International Diabetes Federation (IDF) and Eli Lilly ... together for the second phase of the Bringing Research ... 2), reaffirming their commitment to helping people with diabetes ...
Breaking Medicine Technology: