Twist1 Necessary For Squamous Cell Tumor Formation and Progression

MedicalResearch.com Interview with :
Cédric Blanpain, MD, PhD

Professor of Stem Cell and Developmental Biology
WELBIO, Interdisciplinary Research Institute (IRIBHM)
Université Libre de Bruxelles
Belgium

MedicalResearch.com : What is the background for this study? What are the main findings?

Dr. Blanpain: 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 tumor growth. These cells could be resistant to therapy thus being responsible for tumor relapse after therapy. However, still very little is known about the mechanisms that regulate Cancer stem cells functions.

In a new study published and making the cover of Cell Stem Cell, researchers led by Pr. Cédric Blanpain, MD/PhD, 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 tumor 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 tumor initiation, cancer stem cell function and tumor 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.

The authors demonstrate that different levels of Twist1 are necessary for tumor initiation and progression. Low level of Twist1 is required for the initiation of benign tumors, while higher level of Twist1 is necessary for tumor progression. They also demonstrate that Twist1 is essential for tumor 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.

MedicalResearch.com : What should clinicians and patients take away from your report?

Dr. Blanpain: This work shows that Twist1, a well-known regulator of tumor progression, is necessary for tumor 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 tumor 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. As it is quite difficult to specifically target transcription factors like Twist1 with pharmacological compounds, it will be important to investigate the importance of Twist1 target genes.

MedicalResearch.com : What recommendations do you have for future research as a result of this study?

Dr. Blanpain: As we mentioned above, it will be important to investigate the importance of Twist1 target genes such as those encoding receptors or metabolism related enzyme for which inhibitors may be developed. This study already identified one receptor and one enzyme that are both important for tumorigenesis and may therefore constitute good candidates. Moreover, the dose dependent role of Twist1 on tumor progression is intriguing and it will be therefore important to further investigate the set of genes regulated by Twist1 at low and high dose as well as the mechanisms involved in the regulation of Twist1 expression during carcinogenesis.

Citation:

Different Levels of Twist1 Regulate Skin Tumor Initiation, Stemness, and Progression
Cell Stem Cell Volume 16, Issue 1, 8 January 2015, Pages 67–79
Benjamin Beck Gaëlle Lapouge Sandrine Rorive Benjamin Drogat Kylie Desaedelaere Stephanie Delafaille Christine Dubois Isabelle Salmon Karen Willekens Jean-Christophe Marine Cédric Blanpain