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Study identifies an oncogene causing skin cancer and abnormal proliferation of stem cells


Dj, 03/02/2011 - 18:00

Study identifies an oncogene causing skin cancer and abnormal proliferation of stem cells

CRG researchers in collaboration with Cold Spring Harbor Laboratory, NY, identify the p63 gene as an oncogene that drives squamous cell carcinoma and show how it promotes stem cell survival during tumor development. 
The work, published in Cell Stem Cell, shows these results on February 4,  World Cancer Day.
The p63 gene is frequently overexpressed in squamous cell carcinoma from a number of tissues including head and neck, skin and lung. Scientists already knew about its presence in cancer cells but its role was not clear. While some evidence pointed to p63 as a cancer promoter, other evidence suggested quite the opposite, and presented p63 as a cancer protector. 
The function of p63 in tumor development had been complicated by the existence of multiple different subtypes, or isoforms of the protein. Bill Keyes, formerly at Cold Spring Harbor Laboratory in the United States and now head of the Mechanisms of Cancer and Aging group at the Centre for Genomic Regulation in Barcelona, Spain, previously helped to describe the role of one of the p63 isoforms as a protector gene in cancer development in a paper published in Nature Cell Biology. Now, his team at the Centre for Genomic Regulation and the team led by Dr. Alea Mills at Cold Spring Harbor Laboratory, describe the causative function of another subtype of p63, Np63 in tumor development, answering a long standing question about squamous cell carcinoma development and completing the puzzle of p63´s functions in cancer.
Stem cells and cancer
In the study, Keyes et al found that this gene promotes tumor development by inhibiting cellular senescence, a powerful tumor protective mechanism that normally prevents cells from becoming cancerous. “Unfortunately there are a number of genetic events that can prevent senescence and push a cell down the road towards cancer. When Np63 is expressed at higher levels than normal, it is able to do this” says Dr. Mills. However, the researchers further noticed that the cells escaping senescence exhibited distinct growth properties, much like normal stem cells. “We all have stem cells in our bodies in charge of regenerating and maintaining our tissues. We have seen that Np63 promotes survival of a population of stem cells in the skin during tumor development” explains Bill Keyes, first author of this work. “A current idea receiving much attention is the parallelism between stem cells and cancerous cells. While many scientists study cancer cells and compare them with normal stem cells, here we have looked at the normal stem cells to understand how these cells could become cancerous” adds Dr. Keyes.
The study also uncovers a new key player for the whole process in a protein called Lsh. This protein, which is important for chromatin remodeling and epigenetic changes, was found to be essential for the early stages. “Finding not only the role of p63 in cancer but also the involvement of Lsh is very exciting. It could be a good target to focus on new treatments for skin and other cancers in the future” states Keyes. 
Notes for editors:
Reference work: Keyes et al. Np63 Is an Oncogene that Targets Chromatin Remodeler Lsh to Drive Skin Stem Cell Proliferation and Tumorgenesis, Cell Stem Cell (2011), doi:10.1016/j.stem.2010.12.009
For further information: Laia Cendrós, Centre for Genomic Regulation (CRG). Tel. +34 93 316 02 37.