Researchers have been trying to identify the cells at the origin of cancer and to understand the molecular changes that occur in tumour-initiating cells from the first oncogenic mutation to the development of invasive cancer. The most diagnosed cancer in humans is basal cell carcinoma, with over a million such cases reported each year. A European-funded team of researchers has finally uncovered the cells at the origin of basal cell carcinoma.
A European Research Council (ERC) Starting Grant worth EUR 1.6 million was awarded to Professor Cédric Blanpain of the Université libre de Bruxelles (ULB). The finding was recently presented in the journal Nature Cell Biology.
Professor Blanpain led a team that dissected for the first time the molecular changes occurring in basal cell carcinoma-initiating cells from the first oncogenic mutation to the development of invasive cancer.
Khalil Kass Youssef, the lead author of the study, and colleagues discovered that the cells at the origin of the basal cell carcinoma were initially reprogrammed into embryonic hair follicle progenitor-like fate before they progressed into invasive carcinoma. 'We were extremely surprised to see that tumor initiating cells were progressively and profoundly reprogram into a molecular identity that resemble to progenitor cells presented during embryonic development,' said Dr Youssef.
The scientists showed that the Wnt/beta-catenin signalling pathway is activated in basal cell carcinoma-initiating cells just after oncogene expression. The team established that Wnt/beta-catenin signalling is needed for the reprogramming of tumour-initiating cells into embryonic hair follicle progenitors and for tumour initiation after using genetic or pharmacologic inhibition of the Wnt/beta-catenin signalling.
Professor Blanpain’s team, which worked together with physicians from the Department of Dermatology, Pathology and Plastic Surgery at the Hospital Erasme, indicated that human basal cell carcinomas also show signs of reprogramming into embryonic hair follicle progenitors and activating of the Wnt/beta-catenin signalling. Their discovery confirmed how important this pathway is for human patients.
'I am particularly excited about this work, because this basic research turns out to be very relevant for human diseases, with the identification of potentially new avenues to treat or to prevent the occurrence of the most common cancer in humans,' said Professor Blanpain.
This research study will help develop other work in cancer, development and stem cell biology.
Other funding for this study came from the Fonds de la Recherche Scientifique (FNRS), the program d’excellence CIBLES of the Wallonia Region, a research grant from the Fondation contre le Cancer, the Fondation ULB, the Fonds Yvonne Boël, the Fond Gaston Ithier and the EMBO Young Investigator Programme.