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Relationship Found between Cancer Genes and the Reprogramming Gene SOX2

A team of researchers from the Spanish National Cancer Research Centre (CNIO), led by Dr. Manuel Serrano, from the Tumour Suppression Group, together with scientists from London and Santiago de Compostela, has discovered that the cellular reprogramming gene SOX2, which is involved in several types of cancers, such as lung cancer and pituitary cancer, is directly regulated by the tumor suppressor CDKN1B(p27) gene, which is also associated with these types of cancer. The same December 7, 2012 edition of Cell Stem Cell also includes a study led by Dr. Massimo Squatrito, who recently joined the CNIO to direct the Seve Ballesteros Foundation Brain Tumour Group. This study, carried out in Dr. Eric C. Holland's laboratory, at the Memorial Sloan Kettering Cancer Center (MSKCC), in New York, shows the relationship between MEF, a gene regulator involved in glioblastomas - the most aggressive and common brain tumors -, and SOX2. The cell reprogramming process, discovered by this year's Nobel Prize co-winner, Dr. Shinya Yamanaka, has become a powerful tool for researchers. Via the introduction of a cocktail of four genes, among them SOX2, into cells, scientists can reprogram cells and transform them into stem cells which can be used to study a variety of processes, including cancer. The research team led by Dr. Serrano and Dr. Manuel Collado was interested in the possible role of the tumor suppressor gene CDKN1B(p27) in reprogramming. During the course of these studies, Dr. Han Li, first author of the study, unexpectedly discovered that cells deficient in the CDKN1B(p27) gene could be reprogrammed without the need to introduce SOX2. This observation was the starting point to unravel the functional relationship between the two genes. The work led by Dr. Squatrito, in which Dr. Elena Bazzoli figures as first author, was based on earlier works that linked SOX2 with tumorigenesis. The article describes how SOX2 is regulated by MEF in cells of the nervous system. "Brain tumour cells acquire stem cell traits thanks to the participation of SOX2, and this produces an increase in tumorigenic potential" states Dr. Squatrito. These new insights help to explain the origin of cancers linked to CDKN1B(p27) and MEF, and highlight the potential role of adult stem cells in cancer. Image shows expression of SOX2 protein (red) and the neuronal marker NF1 (green). [Press release] [Cancer Stem Cell abstract (Serrano)] [Cancer Stem Cell abstract (Squatrito)]