molecular mechanisms regulating tumor initiation in the SCC of the skin exposed -
advanced online publication in Nature: Researchers at the Free University of Brussels, ULB discover the molecular mechanisms regulating tumor initiation and stem cancer cell functions in squamous cell carcinoma of the skin.
squamous cell carcinoma (SCC) is the second cancer the most common skin with over half a million new patients each year affected the world. The cancer stem cells (CMCs) a population of cancer cells that have been described in many different cancers, including the SCC of the skin and that the supply growth of a tumor, may be resistant to treatment therefore be responsible for tumor relapse after therapy. However, still very little is known about the mechanisms that regulate the functions of CCM in this cancer.
In a new study published in Nature, researchers led by Professor. Cedric Blanpain, MD / PhD, professor and WELBIO researcher IRIBHM, Free University of Brussels, Belgium, demonstrate an essential role for the factor Sox2 transcription in the regulation of cellular functions initiation of the tumor and cancer stem in squamous cell carcinoma of the skin.
state of art genetic mouse models Boumahdi Soufiane and his colleagues used to dissect, step by step, the functional role and molecular mechanisms by which Sox2 controls the initiation of stem cell functions of the tumor and cancer in skin tumors. In collaboration with physicians Department of Pathology (Dr Sandrine Rorive and Prof. Isabelle Salmon) and the Dermatology department (Pr Véronique del Marmol) at Hôpital Erasme, they showed that Sox2 - one of the four genes used by the Pr. Yamanaka, Nobel laureate, 2012, reprogramming differentiated cells to pluripotent stem cells, which is a transcription factor known to control the function of a wide range of normal stem cells- was absent from the normal epidermis began to be expressed in the early stages of skin cancer in mice and man. In collaboration with the laboratory of epigenetics and cancer (Pr François Fuks), they showed that Sox2 is epigenetic regulated. They showed that the removal of Sox2 prevents the initiation of skin cancer that demonstrates the essential role of Sox2 during tumorigenesis.
Using genetic tools to isolate cells expressing Sox2 of skin cancer, Soufiane Boumahdi and colleagues found that Sox2 mark a population of cancer stem cells with increased capacity to reform the tumor when transplantation. Removal of the population of cancer cells Sox2 positive results in rapid shrinkage of tumors, demonstrating for the first time that Sox2 mark a population of cells that play a critical role in maintaining the in vivo tumor in their natural environment . "It was really amazing to see how fast the tumors diminished and eventually disappeared completely eliminating only a subpopulation of cancer cells," said Soufiane Boumahdi, the first author of this study.
The researchers found a new strain of biomarkers expressed by cancer cells positive cells Sox2 that can potentially be used in the future to identify new predictive markers in cancer and / or to develop new therapeutic strategies to remove or alter the cancer stem cells. They also discovered a new gene network regulated by Sox2 that controls many essential aspects of cancer functions.
In conclusion, this work identifies Sox2 as marking a continuum in tumorigenesis skin from the early stages of cancer initiation to the control of cell functions cancer stem in invasive cancer. "It is fascinating to see how cancer cells reuse some of the normal development programs to support their growth and expansion. In addition, given the wide variety of cancers expressing Sox2, identification of new markers expressed by Sox2 positive cancer stem cells and genes regulated by Sox2 to support the proliferation and progression of skin cancers are likely to be relevant to other cancers and to develop new strategies to target cancer stem cells. "comments Prof. Cedric Blanpain, last and corresponding author of the study.
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