Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition

  • Authors:
    • Xue Wang
    • Hui Cui
    • Zhongguan Lou
    • Shuaishuai Huang
    • Yu Ren
    • Ping Wang
    • Guobin Weng
  • View Affiliations

  • Published online on: April 27, 2017     https://doi.org/10.3892/mmr.2017.6519
  • Pages: 4191-4198
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Abstract

Renal cell carcinoma (RCC) is the most frequently occurring malignancy of the kidney worldwide. Anti-angiogenic targeted therapies inhibit the progression of RCC, however, limited effects on the invasion or metastasis of tumor cells have been observed. Cyclic AMP responsive element‑binding protein (CREB) is a serine/threonine kinase that has been implicated in the regulation of cell proliferation, apoptosis, cycle progression and metastasis, amongst others. Our previous research demonstrated that phosphorylated CREB (pCREB) was upregulated in human renal cancer cell lines and tissues, and decreased pCREB at the Ser133 site inhibited the growth and metastatic activity of OS‑RC‑2 cells. However, the role of CREB in RCC metastasis requires further investigation. Thus, the present study further investigated the role of CREB in RCC metastasis. The present study demonstrated that knockdown of CREB using small interfering RNA (siRNA) that targeted CREB (siCREB) significantly inhibited the migration and invasion of 786‑O and OS‑RC‑2 cells, however, the opposite effect was observed in ACHN cells. In addition, knockdown of CREB suppressed the expression of matrix metallopeptidase (MMP)‑2/9 and proteins associated with epithelial‑mesenchymal transition (EMT) in 786‑O and OS‑RC‑2 cells, and promoted expression in ACHN cells. Furthermore, the chromatin immunoprecipitation assay indicated that pCREB (Ser133) had a direct interaction with the fibronectin promoter, however, pCREB (Ser133) did not target the vimentin promoter in RCC. Therefore, the results of the present study indicate that CREB regulated metastatic RCC by mediating the expression of MMP‑2/9 and EMT‑associated proteins, however, CREB‑mediated MMP‑2/9 and EMT‑associated protein expression may be induced by different pathways in different RCC cells.
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June-2017
Volume 15 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang X, Cui H, Lou Z, Huang S, Ren Y, Wang P and Weng G: Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition. Mol Med Rep 15: 4191-4198, 2017
APA
Wang, X., Cui, H., Lou, Z., Huang, S., Ren, Y., Wang, P., & Weng, G. (2017). Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition. Molecular Medicine Reports, 15, 4191-4198. https://doi.org/10.3892/mmr.2017.6519
MLA
Wang, X., Cui, H., Lou, Z., Huang, S., Ren, Y., Wang, P., Weng, G."Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition". Molecular Medicine Reports 15.6 (2017): 4191-4198.
Chicago
Wang, X., Cui, H., Lou, Z., Huang, S., Ren, Y., Wang, P., Weng, G."Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition". Molecular Medicine Reports 15, no. 6 (2017): 4191-4198. https://doi.org/10.3892/mmr.2017.6519