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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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Beck B,Lapouge G,Rorive S,Drogat B,Desaedelaere K,Delafaille S,Dubois C,Salmon I,Willekens K,Marine JC,Blanpain C

doi

10.1016/j.stem.2014.12.002

subject

Has Abstract

pub_date

2015-01-08 00:00:00

pages

67-79

issue

1

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(14)00560-8

journal_volume

16

pub_type

杂志文章

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