title: Different levels of Twist1 regulate skin tumor initiation, stemness, and progression.
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.
authors.affiliation: Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Beck
authors.affiliation: Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Lapouge
authors.affiliation: Department of Pathology, Erasme Hospital, ULB, 1070 Brussels, Belgium; DIAPATH - Center for Microscopy and Molecular Imaging (CMMI), 6041 Gosselies, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rorive
authors.affiliation: Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drogat
authors.affiliation: Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Kylie
authors.initials: K
authors.lastname: Desaedelaere
authors.affiliation: Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Delafaille
authors.affiliation: Université Libre de Buxelles (ULB), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Dubois
authors.affiliation: Department of Pathology, Erasme Hospital, ULB, 1070 Brussels, Belgium; DIAPATH - Center for Microscopy and Molecular Imaging (CMMI), 6041 Gosselies, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
authors.affiliation: 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.
authors.forename: Karen
authors.initials: K
authors.lastname: Willekens
authors.affiliation: 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.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marine
authors.affiliation: 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.
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D055550:Protein Stability; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse