PKCδ maintains phenotypes of tumor initiating cells through cytokine-mediated autocrine loop with positive feedback.
Oncogene
; 34(46): 5749-59, 2015 Nov 12.
Article
en En
| MEDLINE
| ID: mdl-25746003
ABSTRACT
The existence of tumor initiating cells (TICs) has been emerged as a good therapeutic target for treatment of glioblastoma that is the most aggressive brain tumor with poor prognosis. However, the molecular mechanisms that regulate the phenotypes of TICs still remain obscure. In this study, we found that PKCδ, among PKC isoforms, is preferentially activated in TICs and acts as a critical regulator for the maintenance of TICs in glioblastoma. By modulating the expression levels or activity of PKCδ, we demonstrated that PKCδ promotes self-renewal and tumorigenic potentials of TICs. Importantly, we found that the activation of PKCδ persists in TICs through an autocrine loop with positive feedback that was driven by PKCδ/STAT3/IL-23/JAK signaling axis. Moreover, for phenotypes of TICs, we showed that PKCδ activates AKT signaling component by phosphorylation specifically on Ser473. Taken together, we proposed that TICs regulate their own population in glioblastoma through an autocrine loop with positive feedback that is driven by PKCδ-dependent secretion of cytokines.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
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Glioblastoma
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Comunicación Autocrina
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Proteína Quinasa C-delta
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2015
Tipo del documento:
Article