Scientists have discovered 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 study, 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.
The findings could also aid efforts to grow skin grafts and treat burn patients.
“We have found a molecular switch that tells your skin to keep growing or stop growing,” said Fernando Camargo at Children’s Hospital Boston.
Camargo and colleagues manipulated a molecule called Yap1 to cause massive tumor growth by triggering a pathway known as Hippo.
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.
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.
The study is published in Cell. (ANI)
Yap1 Acts Downstream of ?-Catenin to Control Epidermal Proliferation; Karin Schlegelmilch, Morvarid Mohseni, Oktay Kirak, Jan Pruszak, J. Renato Rodriguez, Dawang Zhou, Bridget T. Kreger, Valera Vasioukhin, Joseph Avruch, Thijn R. Brummelkamp, Fernando D. Camargo; Cell – 4 March 2011 (Vol. 144, Issue 5, pp. 782-795)