E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells.
Int J Oncol
; 53(2): 567-578, 2018 Aug.
Article
en En
| MEDLINE
| ID: mdl-29901191
ABSTRACT
Colorectal cancer (CRC) is a type of cancer with a mortality rate among the highest worldwide owing to its high rate of metastasis. Therefore, inflammation-associated metastasis in the development of CRC is currently a topic of considerable interest. In the present study, the pro-inflammatory cytokine interleukin-4 (IL-4) was identified to promote the epithelial-mesenchymal transition (EMT) of CRC cells. However, the enhancing effect of IL-4 was more evident in HCT116 cells compared with in RKO cells. Accordingly, an increased expression level of STAT6 was observed in HCT116 cells compared with RKO cells. Further investigations identified that E2F1 was required for maintaining the level of signal transducer and activator of transcription 6 (STAT6) in HCT116 cells. Mechanistically, E2F1 induced specificity protein 3 (SP3) directly by binding to the promoter of the STAT6 gene and activating its transcription in CRC cells. As a result, phosphorylation-activated STAT6 increased the expression of several EMT drivers, including zinc finger E-box-binding homeobox (Zeb)1 and Zeb2, which serve a critical function in IL-4-induced EMT. Rescue experiments further confirmed that IL-4-induced EMT relied on an intact E2F1/SP3/STAT6 axis in CRC cells. Finally, analysis of clinical CRC specimens revealed a positive correlation between E2F1, SP3 and STAT6. The ectopically expressed E2F1/SP3/STAT6 axis indicated a poor prognosis in patients with CRC. In conclusion, the E2F1/SP3/STAT6 pathway was identified to be essential for IL-4 signaling-induced EMT and aggressiveness of CRC cells.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
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Interleucina-4
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Factor de Transcripción STAT6
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Factor de Transcripción Sp3
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Factor de Transcripción E2F1
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2018
Tipo del documento:
Article