Implication of Ataxia-Telangiectasia-mutated kinase in epithelium-mesenchyme transition.
Carcinogenesis
; 42(4): 640-649, 2021 04 30.
Article
en En
| MEDLINE
| ID: mdl-33417668
ABSTRACT
Impairment of genome instability drives the development of cancer by disrupting anti-cancer barriers. Upon genotoxic insults, DNA damage responsive factors, notably ATM kinase, is crucial to protect genomic integrity while promoting cell death. Meanwhile, cytotoxic therapy-inducing DNA lesions is double-edged sword by causing cancer metastasis based on animal models and clinical observations. The underlying mechanisms for the procancer effect of cytotoxic therapies are poorly understood. Here, we report that cancer cells subjected to cytotoxic treatments elicit dramatic alteration of gene expression controlling the potential of epithelium-mesenchyme transition (EMT). Resultantly, EMT-dependent cell mobility is potently induced upon DNA damage. This stimulation of EMT is mainly Ataxia-Telangiectasia-mutated (ATM)-dependent, as the chemical inhibitor specifically inhibiting ATM kinase activity can suppress the EMT gene expression and thus cell mobility. At last, we show that cancer cells with ATM activation display increased metastatic potential in ovarian cancer tissues. Taken together, we reveal a novel role of ATM in promoting metastatic potential of cancer cells by favoring EMT gene expression.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proliferación Celular
/
Transición Epitelial-Mesenquimal
/
Proteínas de la Ataxia Telangiectasia Mutada
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Carcinogenesis
Año:
2021
Tipo del documento:
Article