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
Toyonobu MaedaYasumasa Kato

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.

References

Mar 1, 1996·Clinical & Experimental Metastasis·R Martínez-ZaguilánM J Hendrix
Jul 13, 2001·Clinical & Experimental Metastasis·N ChandrasekarS Mohanam
Apr 12, 2002·The Journal of Biological Chemistry·Huasheng LuAjay Verma
Dec 4, 2003·Experimental Cell Research·Irina AbécassisAïda Karniguian
Dec 4, 2003·Melanoma Research·Christian RiebelingChristoph C Geilen
Aug 6, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·George A SarosiRhonda F Souza
May 19, 2006·Cancer Research·Robert A GatenbyRobert J Gillies
Oct 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michaël Lora-MichielsMark W Dewhirst
Feb 28, 2008·Clinical & Experimental Metastasis·Raymond E MoelleringRobert J Gillies
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chihiro MogiFumikazu Okajima
Mar 12, 2009·Cancer Research·Ian F RobeyRobert J Gillies
Jun 23, 2009·Cellular Immunology·Naoya MurataFumikazu Okajima
Jul 26, 2011·Cold Spring Harbor Symposia on Quantitative Biology·G L Semenza
Aug 6, 2011·PloS One·Anne RiemannMichael Gekle
Apr 30, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yoon-Jin LeeSang-Han Lee
Sep 6, 2013·Cancer Cell International·Yasumasa KatoYuh Baba
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
May 3, 2014·Seminars in Oncology·Joseph M CurryMadalina Tuluc
Sep 24, 2014·Pharmacological Reviews·Ronald C BruntzH Alex Brown
Dec 11, 2014·Cancer Cell International·Atsuko SuzukiYasumasa Kato
Jan 13, 2015·Biochemical and Biophysical Research Communications·Yuta MochimaruHideaki Tomura
Apr 9, 2015·Bone Reports·Toyonobu MaedaYasumasa Kato

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Citations

Feb 20, 2020·Biological Reviews of the Cambridge Philosophical Society·Yuanfa YaoYingke Xu
Mar 7, 2019·Scientific Reports·Matteo Bolomini-VittoriAlessandra Cambi

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