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Title: Different Levels of Twist1 Regulate Skin Tumor Initiation, Stemness, and Progression
Authors: Beck, Benjamin ×
Lapouge, Gaelle
Rorive, Sandrine
Drogat, Benjamin
Desaedelaere, Kylie
Delafaille, Stephanie
Dubois, Christine
Salmon, Isabelle
Willekens, Karen
Marine, Chris
Blanpain, Cedric #
Issue Date: Jan-2015
Publisher: Cell Press
Series Title: Cell Stem Cell
Abstract: Twist1 promotes epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and cancer stem cell (CSC) properties. However, it remains unclear whether Twist1 is also required for tumor initiation and whether Twist1-induced cancer stemness and EMT are functionally linked. Using a conditional deletion of Twist1 at different stages of skin carcinogenesis, we show that Twist1 is required for skin tumor initiation and progression in a gene-dosage-dependent manner. Moreover, conditional ablation of Twist1 in benign tumors leads to increased apoptosis, reduced cell proliferation, and defective tumor maintenance and propagation independently of its EMT-inducing abilities. Concomitant deletion of Twist1 and p53 rescues the apoptotic response, but not the cell proliferation and propagation defects. These results reveal that Twist1 is required for tumor initiation and maintenance in a p53-dependent and -independent manner. Importantly, our findings also indicate that tumor stemness and EMT can be regulated by distinct mechanisms.
ISSN: 1934-5909
Publication status: accepted
KU Leuven publication type: IT
Appears in Collections:Laboratory for Molecular Cancer Biology
× corresponding author
# (joint) last author

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