2 min readSkin Cancer : New Mechanism Involved in Tumour Initiation, Growth and Progression

Brussel, Belgium — Researchers at the Université libre de Bruxelles (Belgium) have reported the mechanisms regulating the different functions of Twist1 controlling skin tumour initiation, cancer stem cell function and tumour progression.

Squamous cell carcinoma (SCC) represents the second most frequent skin cancer with more than half million new patients affected every year in the world. Cancer stem cells (CSCs) are a population of cancer cells that have been described in many different cancers, including skin SCCs and that feed tumour growth, could be resistant to therapy thus being responsible for tumour relapse after therapy. However, still very little is known about the mechanisms that regulate CSCs functions.
 
In a new study published and making the cover of Cell Stem Cell, researchers led by Professor Cédric Blanpain, professor and WELBIO investigator at the IRIBHM, Université libre de Bruxelles, Belgium, report the mechanisms regulating the different functions of Twist1 controlling skin tumour initiation, cancer stem cell function and tumour progression.

Benjamin Beck and colleagues used state of the art genetic mouse models to dissect, the functional role and molecular mechanisms by which Twist1 controls tumour initiation, cancer stem cell function and tumour progression. In collaboration with Dr. Sandrine Rorive and Pr Isabelle Salmon from the department of Pathology at the Erasme Hospital, ULB and the group of Jean-Christophe Marine (VIB, KUL Leuven), they demonstrated that while Twist1 is not expressed in the normal skin, Twist1 deletion prevents skin cancer formation demonstrating the essential role of Twist1 during tumorigenesis. “It was really surprising to observe the essential role of Twist1 at the earliest step of tumour formation, as Twist1 was thought to stimulate tumour progression and metastasis” comments Benjamin Beck, the first author of this study.

The authors demonstrate that different levels of Twist1 are necessary for tumour initiation and progression. Low level of Twist1 is required for the initiation of benign tumours, while higher level of Twist1 is necessary for tumour progression. They also demonstrate that Twist1 is essential for tumour maintenance and the regulation of cancer stem cell function. The researchers also uncovered that the different functions of Twist1 are regulated by different molecular mechanisms, and identified a p53 independent role of Twist1 in regulating cancer stem cell functions.

In conclusion, this work shows that Twist1, a well-known regulator of tumour progression, is necessary for tumour initiation, regulation of cancer stem cell function and malignant progression. “It was really interesting to see that different levels of Twist1 are required to carry out these different tumour functions and that these different Twist1 functions are regulated by different molecular pathways.  Given the diversity of cancers expressing Twist1, the identification of the different mechanisms controlled by Twist1 are likely to be relevant for other cancers” comments Cédric Blanpain, the last and corresponding author of this study.

Article adapted from a Libre de Bruxelles, Université news release.

Publication: Different Levels of Twist1 Regulate Skin Tumor Initiation, Stemness, and Progression. Benjamin Beck, Gaëlle Lapouge, Sandrine Rorive, Benjamin Drogat, Kylie Desaedelaere, Stephanie Delafaille, Christine Dubois, Isabelle Salmon, Karen Willekens, Jean-Christophe Marine, Cédric Blanpain. Cell Stem Cell (2015): Click here to view.

Oncogenomics

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