Scientists from free University of Brussel have indicated that Twist1 could regulate the skin cancer‘s propagation and the function of cancer stem cells to suppress the deterioration process. They use transgenetic mice as the subjects, successfully identified the molecular of cancer’s initiation, propagation, and deterioration. This study was published in Cell Stem Cell.

The epithelial-to-mesenchymal transition(EMT) is a cellular process during which epithelial cells lose their adhesion properties and acquire mesenchymal features allowing their migration and invasion.Twist1, a basic-helix-loop-helix transcription factor, is one of the EMT-inducer prototypes. Twist1 deletion in mice leads to failure in neural tube closure associated with defects in the formation of the head mesenchyme and limb buds.

Mechanistically, Twist1 overexpression has been shown to rescue Myc-induced apoptosis through inhibition of p53. However, to what extent these different functions of Twist1 including its effect on EMT, stemness, proliferation, and apoptosis are functionally linked or whether these functions are independently regulated by Twist1 remians unknown.

In this study, using conditional deletion of Twist1 at different stages of skin tumorigenesis, researchers investigated the different functions of Twist1 and their interdependence during tumor initiation, maintenance, propagation, and malignant progression. They found that Twist1 is expressed at the earliest step of tumorigenesis and is essential for the initiation and maliganant progression of skin tumors in a gene-dosage-dependent manner. Conditional deletion of Twist1 in pre-existing tumors demonstrates the essential role of Twist1 in tumor maintenance. Twist1 inhibits oncogene-induced apoptosis in a p53-dependent manner, while the ability of Twist1 to promote tumor cell proliferation and propagation is regulated by a p53-in-dependent mechanism. Strikingly, these oncogenic functions of Twist are not dependent upon its ability to induce EMT.

Reference:

Beck B, Lapouge G, Rorive S, et al. Different Levels of Twist1 Regulate Skin Tumor Initiation, Stemness, and Progression[J]. Cell stem cell, 2015, 16(1): 67-79.