Open Access

NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells

  • Authors:
    • Suneetha Amara
    • Dalal Alotaibi
    • Venkataswarup Tiriveedhi
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  • Published online on: June 15, 2016     https://doi.org/10.3892/ol.2016.4713
  • Pages: 933-943
  • Copyright: © Amara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic inflammation has been considered an important player in cancer proliferation and progression. High salt (sodium chloride) levels have been considered a potent inducer of chronic inflammation. In the present study, the synergistic role of high salt with interleukin (IL)‑17 towards induction of the inflammatory and angiogenic stress factor vascular endothelial growth factor (VEGF)‑A was investigated. Stimulation of MCF-7 breast cancer cells with high salt (0.2 M NaCl) and sub‑minimal IL‑17 (1 ng/ml) enhanced the expression of VEGF-A (2.9 and 2.6-fold, respectively, P<0.05) compared with untreated cells. Furthermore, co‑treatment with both high salt and sub‑minimal IL‑17 led to a 5.9‑fold increase in VEGF‑A expression (P<0.01), thus suggesting a synergistic role of these factors. VEGF‑A promoter analysis and specific small interfering RNA knock‑down of transcription factors revealed that high salt induced VEGF‑A expression through nuclear factor of activated T‑cells (NFAT)5, while IL‑17 induced VEGF‑A expression via signal transducer and activator of transcription (STAT)3 signaling mechanisms. Treatment of normal human aortic endothelial cells with the supernatant of activated MCF‑7 cells enhanced cell migration and induced expression of migration‑specific factors, including vascular cell adhesion protein, β1 integrin and cluster of differentiation 31. These data suggest that high salt levels synergize with pro‑inflammatory IL‑17 to potentially induce cancer progression and metastasis through VEGF‑A expression. Therefore, low‑salt diet, anti‑NFAT5 and anti‑STAT3 therapies may provide novel avenues for enhanced efficiency of the current cancer therapy.
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August-2016
Volume 12 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Amara S, Alotaibi D and Tiriveedhi V: NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells. Oncol Lett 12: 933-943, 2016
APA
Amara, S., Alotaibi, D., & Tiriveedhi, V. (2016). NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells. Oncology Letters, 12, 933-943. https://doi.org/10.3892/ol.2016.4713
MLA
Amara, S., Alotaibi, D., Tiriveedhi, V."NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells". Oncology Letters 12.2 (2016): 933-943.
Chicago
Amara, S., Alotaibi, D., Tiriveedhi, V."NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells". Oncology Letters 12, no. 2 (2016): 933-943. https://doi.org/10.3892/ol.2016.4713