IKKß-Mediated Resistance to Skin Cancer Development Is Ink4a/Arf-Dependent.
Mol Cancer Res
; 15(9): 1255-1264, 2017 09.
Article
en En
| MEDLINE
| ID: mdl-28584022
ABSTRACT
IKKß (encoded by IKBKB) is a protein kinase that regulates the activity of numerous proteins important in several signaling pathways, such as the NF-κB pathway. IKKß exerts a protumorigenic role in several animal models of lung, hepatic, intestinal, and oral cancer. In addition, genomic and proteomic studies of human tumors also indicate that IKBKB gene is amplified or overexpressed in multiple tumor types. Here, the relevance of IKKß in skin cancer was determined by performing carcinogenesis studies in animal models overexpressing IKKß in the basal skin layer. IKKß overexpression resulted in a striking resistance to skin cancer development and an increased expression of several tumor suppressor proteins, such as p53, p16, and p19. Mechanistically, this skin tumor-protective role of IKKß is independent of p53, but dependent on the activity of the Ink4a/Arf locus. Interestingly, in the absence of p16 and p19, IKKß-increased expression favors the appearance of cutaneous spindle cell-like squamous cell carcinomas, which are highly aggressive tumors. These results reveal that IKKß activity prevents skin tumor development, and shed light on the complex nature of IKKß effects on cancer progression, as IKKß can both promote and prevent carcinogenesis depending on the cell type or molecular context.Implications The ability of IKKß to promote or prevent carcinogenesis suggests the need for further evaluation when targeting this protein. Mol Cancer Res; 15(9); 1255-64. ©2017 AACR.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Inhibidor p16 de la Quinasa Dependiente de Ciclina
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Proteína p14ARF Supresora de Tumor
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Quinasa I-kappa B
Límite:
Animals
Idioma:
En
Revista:
Mol Cancer Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
España