Mitochondrial dysfunction induces EMT through the TGF-β/Smad/Snail signaling pathway in Hep3B hepatocellular carcinoma cells

  • Authors:
    • Eui-Yeun Yi
    • Shi-Young Park
    • Seung-Youn Jung
    • Won-Jun Jang
    • Yung-Jin Kim
  • View Affiliations

  • Published online on: September 10, 2015     https://doi.org/10.3892/ijo.2015.3154
  • Pages: 1845-1853
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Abstract

Mitochondrial dysfunction has been found to be associated with various pathological conditions, particularly cancer. However, the mechanisms underlying tumor malignancy induced by mitochondrial dysfunction are not fully understood. In the present study, the effects of mitochondrial dysfunction on epithelial-mesenchymal transition (EMT), were investigated using mitochondrial-depleted ρ0 cells derived from the Hep3B hepatocarcinoma cell line. The Hep3B/ρ0 cells displayed the EMT phenotype with more aggressive migration and higher invasiveness compared to their parental cells. The Hep3B/ρ0 cells also showed typical expression pattern of EMT markers such as vimentin and E-cadherin. These phenotypes in Hep3B/ρ0 cells were mediated by increased transforming growth factor-β (TGF-β) through the canonical Smad-dependent signaling pathway. Additionally, TGF-β signaling was activated via induction of c-Jun/AP-1 expression and activity. Therefore, mitochondrial dysfunction induces EMT through TGF-β/Smad/Snail signaling via c-Jun/AP-1 activation. These results indicate that mitochondrial dysfunction plays an important role in the EMT process and could be a novel therapeutic target for malignant cancer therapy.
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November-2015
Volume 47 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yi E, Park S, Jung S, Jang W and Kim Y: Mitochondrial dysfunction induces EMT through the TGF-β/Smad/Snail signaling pathway in Hep3B hepatocellular carcinoma cells. Int J Oncol 47: 1845-1853, 2015.
APA
Yi, E., Park, S., Jung, S., Jang, W., & Kim, Y. (2015). Mitochondrial dysfunction induces EMT through the TGF-β/Smad/Snail signaling pathway in Hep3B hepatocellular carcinoma cells. International Journal of Oncology, 47, 1845-1853. https://doi.org/10.3892/ijo.2015.3154
MLA
Yi, E., Park, S., Jung, S., Jang, W., Kim, Y."Mitochondrial dysfunction induces EMT through the TGF-β/Smad/Snail signaling pathway in Hep3B hepatocellular carcinoma cells". International Journal of Oncology 47.5 (2015): 1845-1853.
Chicago
Yi, E., Park, S., Jung, S., Jang, W., Kim, Y."Mitochondrial dysfunction induces EMT through the TGF-β/Smad/Snail signaling pathway in Hep3B hepatocellular carcinoma cells". International Journal of Oncology 47, no. 5 (2015): 1845-1853. https://doi.org/10.3892/ijo.2015.3154