YAP/Aurora A-mediated ciliogenesis regulates ionizing radiation-induced senescence via Hedgehog pathway in tumor cells.
Biochim Biophys Acta Mol Basis Dis
; 1870(4): 167062, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38342416
ABSTRACT
Primary cilia are antenna-like organelles that play critical roles in sensing and responding to various signals. Nevertheless, the function of primary cilia in cellular response to ionizing radiation (IR) in tumor cells remains unclear. Here, we show that primary cilia are frequently expressed in tumor cells and tissues. Notably, IR promotes cilia formation and elongation in time- and dose-dependent manners. Mechanistic study shows that the suppression of YAP/Aurora A pathway contributes to IR-induced ciliogenesis, which is diminished by Aurora A overexpression. The ciliated tumor cells undergo senescence but not apoptosis in response to IR and the abrogation of cilia formation is sufficient to elevate the lethal effect of IR. Furthermore, we show that IR-induced ciliogenesis leads to the activation of Hedgehog signaling pathway to drive senescence and resist apoptosis, and its blockage enhances cellular radiosensitivity by switching senescence to apoptosis. In summary, this work shows evidence of primary cilia in coordinating cellular response to IR in tumor cells, which may help to supply a novel sensitizing target to improve the outcome of radiotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cilios
/
Proteínas Hedgehog
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
China