Abstract
Background:
So far, little research has been conducted regarding the underlying mechanism of renal carcinogenesis at molecular level. Epithelial-mesenchymal transition (EMT) exerts an important part during tumor genesis as well as the development through mitogen-activated protein kinase (MAPK) pathways. Therefore, we hypothesized that EMT could promote renal cell carcinoma (RCC) progression via the ERK5/AP-1pathway.
Materials and methods:
The RCC cell lines were utilized to be the models with in vitro exposure to cigarette smoke extract (CSE). We used the curcumin for the EMT intervention study. In the present study, immunohistochemistry (IHC), Western blotting, and real-time quantitative reverse transcription PCR had been used to determine the experimental results. EMT phenotypic alterations were assessed by changes in cell morphology, invasion and transfer ability, as well as expression of epithelial and mesenchymal markers.
Results:
In human renal cell carcinoma tissue, E-cadherin expression within the smoking renal cancer patients was down-regulated compared with that among the non-smokers. However, Vimentin, N-cadherin, and TWIST levels increased (P<0.05). Significantly, we clarified that ERK5/AP-1 exerted positive regulation on the renal cell carcinoma EMT mediated by CS, which was suggested based on the results of CS activating the ERK5/AP-1 pathway, as well as ERK5 inhibition via XMD8-92 reversed AP-1 protein levels and the EMT process. Furthermore, curcumin showed the same inhibitory effect as XMD8-92 and significantly reversed CS-induced EMT through inhibiting the ERK5/AP-1 signaling pathway.
Conclusion:
The above results indicated that ERK5/AP-1 signaling pathway exerts a vital part for CS-associated RCC development and cancer intervention.
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