A recent report from Children's Hospital Boston reveals how researchers in the Stem Cell Program have discovered a regulator of gene activity that tells epidermal stem cells when to grow more skin or that can sense cell crowding and cease the growth. The work, in mice and human cancer cells, reportedly 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. In addition, it could aid efforts to grow skin grafts and treat burn patients.
The research, published in Cell on March 4, 2011, highlights the relationship between cancer and regeneration. Fernando Camargo, PhD, the study's senior investigator and a principal investigator in Children's Stem Cell Program, and research colleagues manipulated a molecule called Yap1 to cause massive tumor growth by triggering a pathway known as Hippo. According to the report, when they suppressed the Yap1 function in mice, their epidermal skin stem cells failed to expand and they had thin, fragile skin.
The opposite was also true. Activation of Yap1 caused the mice to develop squamous cell carcinoma-like tumors. The researchers 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. According to Camargo, this work suggests that over-activation of Yap 1 is likely what drives these cancers
From these findings, the report suggests that manipulating the Yap 1 molecule could provide ways to grow skin cells when they are needed or, conversely, to stop cancerous growth. Camargo's group is currently 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 investigating other molecules that may also interact with Yap1. For personal care, this work could become applicable in the fields of anti-aging skin care and wound repair.
Karin Schlegelmilch and Morvarid Mohseni of Children's Stem Cell Program and the Harvard Stem Cell Institute were co-first authors of the study. This study was supported by the Stand Up to Cancer-AACR initiative, the National Institutes of Health, the Whitehead Institute Fellows Program, the V Foundation for Cancer Research and the Pew Charitable Trusts.