Survivin is regulated by interleukin-4 in colon cancer stem cells.
J Cell Physiol
; 225(2): 555-61, 2010 Nov.
Article
en En
| MEDLINE
| ID: mdl-20506498
ABSTRACT
Colorectal cancer has provided an important model to test the stem cell hypothesis of cancer origin, which implies that cancer arises as a result of genetic aberrations in stem cells leading to deregulation of the proliferation/differentiation balance. We and others have demonstrated that, similarly to other solid tumors, colon carcinogenesis and progression are dictated by highly apoptosis-resistant stem-like cells. Our data have suggested that protection from apoptosis is achieved by autocrine production of interleukin-4 (IL-4) through up-regulation of anti-apoptotic mediators. In this study, we extend our analysis to another apoptosis inhibitor widely expressed in tumors, namely survivin (also known as BIRC-5, baculoviral IAP repeat-containing protein 5). We show that this protein, with important roles in cell death counteraction and mitotic progression control, is regulated by the IL-4 pathway in colon rectal cancer stem cells (CR-CSC). Hence, the presence of IL-4 increases survivin levels in our model while cytokine neutralization has opposing effects. Treatment with cytokine neutralizing agent or with leflunomide, Stat6 inhibitor, have similar consequences on survivin localization, increasing its nuclear pool, an observation known to be correlated with a good prognosis in colon cancer patients. These results demonstrate that IL-4, through activation of the STAT-6 signaling pathway, is involved in survivin expression levels as well as its localization. These findings shed more light on the molecular mechanisms involved in IL-4-mediated chemoresistance.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
/
Neoplasias Colorrectales
/
Interleucina-4
/
Proteínas Asociadas a Microtúbulos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Cell Physiol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Italia