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Cell Stem Cell. 2015 Jan 8;16(1):67-79. doi: 10.1016/j.stem.2014.12.002.

Different levels of Twist1 regulate skin tumor initiation, stemness, and progression.

Author information

1
Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
2
Department of Pathology, Erasme Hospital, ULB, 1070 Brussels, Belgium; DIAPATH - Center for Microscopy and Molecular Imaging (CMMI), 6041 Gosselies, Belgium.
3
Laboratory for Molecular Cancer Biology, Center for the Biology of Disease, VIB, 3000 Leuven, Belgium; Laboratory for Molecular Cancer Biology, Center of Human Genetics, VIB, 3000 Leuven, Belgium.
4
Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium; WELBIO, 808 route de Lennik, 1070 Brussels, Belgium. Electronic address: cedric.blanpain@ulb.ac.be.

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.

PMID:
25575080
DOI:
10.1016/j.stem.2014.12.002
[Indexed for MEDLINE]
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