RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells

  • Authors:
    • Toyonobu Maeda
    • Satoshi Yuzawa
    • Atsuko Suzuki
    • Yuh Baba
    • Yukio Nishimura
    • Yasumasa Kato
  • View Affiliations

  • Published online on: January 5, 2016     https://doi.org/10.3892/ijo.2016.3322
  • Pages: 1251-1257
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Abstract

Solid tumors are characterized by acidic extracellular pH (pHe). The present study examined the contribution of small GTP-binding proteins to phospholipase D (PLD) activation of acidic pHe-induced matrix metalloproteinase-9 (MMP-9) production. Acidic pHe-induced MMP-9 production was reduced by C3 exoenzyme, which inhibits the Rho family of GTPases; cytochalasin D, which inhibits actin reorganization; and simvastatin, which inhibits geranylgeranylation of Rho. Small interfering RNA (siRNA) against RhoA, but not against Rac1 or Cdc42, significantly inhibited acidic pHe induction of MMP-9. Pull-down assays showed that acidic pHe increased the activated form of RhoA. Forced expression of constitutively active RhoA induced MMP-9 production, even at neutral pHe. RhoA siRNA also reduced acidic pHe induced PLD activity. Specific inhibition of PLD1 and Pld1 gene knockout significantly reduced acidic pHe-induced MMP-9 expression. In contrast, PLD2 inhibition or knockout had no effect on MMP-9 expression. These findings suggested that RhoA-PLD1 signaling is involved in acidic pHe induction of MMP-9.
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March 2016
Volume 48 Issue 3

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

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APA
Maeda, T., Yuzawa, S., Suzuki, A., Baba, Y., Nishimura, Y., & Kato, Y. (2016). RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells. International Journal of Oncology, 48, 1251-1257. https://doi.org/10.3892/ijo.2016.3322
MLA
Maeda, T., Yuzawa, S., Suzuki, A., Baba, Y., Nishimura, Y., Kato, Y."RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells". International Journal of Oncology 48.3 (2016): 1251-1257.
Chicago
Maeda, T., Yuzawa, S., Suzuki, A., Baba, Y., Nishimura, Y., Kato, Y."RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells". International Journal of Oncology 48, no. 3 (2016): 1251-1257. https://doi.org/10.3892/ijo.2016.3322