Uncovering the role of Twist1 in skin cancer initiation, growth and progression

Researchers from Université Libre de Bruxelles (Belgium), led by Cédric Blanpain, have successfully used genetic mouse models to study the functions of Twist1 in skin cancer, while also further investigating the mechanisms regulating these functions. In the study, which was published recently in Cell Stem Cell, the team identified a new mechanism of tumor initiation, growth and progression in squamous cell carcinoma of the skin.

The team concentrated on evaluating the functional role and molecular mechanisms of Twist1, which is involved in the control of skin tumor initiation, cancer stem cell function and tumor progression.

In collaboration with Sandrine Rorive and Isabelle Salmon (both Erasme Hospital, Université Libre de Bruxelles), Blanpain’s team discovered that while Twist1 is not expressed in normal skin, its deletion prevents the formation of skin cancer. The findings demonstrate the potentially crucial function of Twist1 in tumorigenesis.

“It was really surprising to observe the essential role of Twist1 at the earliest step of tumor formation, as Twist1 was thought to stimulate tumor progression and metastasis” commented Benjamin Beck (Université Libre de Bruxelles), the first author of this study.

The authors then went on to demonstrate that different levels of Twist1 are required for tumor initiation and progression. While lower levels of Twist1 are required for the initiation of benign tumors, higher levels of Twist1 are necessary for tumors to progress. Both tumor maintenance and the regulation of cancer stem cell function require that Twist1 be present. They also found that the different functions of Twist1 are controlled by different molecular mechanisms, both dependent and independent of p53.

“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” summarized Cédric Blanpain.

Source: Beck B, Lapouge G, Rorive S et al. Different levels of twist1 regulate skin tumor initiation, stemness, and progression. Cell Stem Cell. 16(1), 67-79 (2015). Université Libre de Bruxelles press release via AlphaGalileo