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

Toyonobu Maeda, Satoshi Yuzawa, Atsuko Suzuki, Yuh Baba, Yukio Nishimura, Yasumasa Kato

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1251-1257
Number of pages7
JournalInternational journal of oncology
Volume48
Issue number3
DOIs
Publication statusPublished - Mar 2016

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Experimental Melanomas
Matrix Metalloproteinase 9
Messenger RNA
Phospholipase D
Small Interfering RNA
Prenylation
Cytochalasin D
rho GTP-Binding Proteins
Gene Knockout Techniques
Simvastatin
phospholipase D1
GTP-Binding Proteins
Actins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells. / Maeda, Toyonobu; Yuzawa, Satoshi; Suzuki, Atsuko; Baba, Yuh; Nishimura, Yukio; Kato, Yasumasa.

In: International journal of oncology, Vol. 48, No. 3, 03.2016, p. 1251-1257.

Research output: Contribution to journalArticle

Maeda, Toyonobu ; Yuzawa, Satoshi ; Suzuki, Atsuko ; Baba, Yuh ; Nishimura, Yukio ; Kato, Yasumasa. / RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells. In: International journal of oncology. 2016 ; Vol. 48, No. 3. pp. 1251-1257.
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