GM3 upregulation of matrix metalloproteinase-9 possibly through PI3K, AKT, RICTOR, RHOGDI-2, and TNF-a pathways in mouse melanoma B16 cells

Pu Wang, Xiaodong Wang, Peixing Wu, Jinghai Zhang, Toshinori Sato, Sadako Yamagata, Tatsuya Yamagata

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Citations (Scopus)

Abstract

Ganglioside GM3 has recently been shown to regulate tumor necrosis factor (TNF)-α at both the transcriptional and translational levels in murine melanoma B16 cells (Wang et al., Biochem Biophy Res Commun 356:438-443, 2007; Wang et al., Oncology 73:430-438, 2007). Since TNF-α is known to stimulate matrix metalloproteinase (MMP)-9 synthesis, which is highly involved in tumor cell metastasis, we considered whether MMP-9 is regulated by GM3. Expression of GM3 in B16 cells was modified by genetic manipulation, exogenous GM3 addition, and inhibition of GM3 synthesis followed by determination of MMP-9 expression by reverse transcriptase-polymerase chain reaction (RT-PCR) and/or gelatin zymography. We determined that MMP-9, but not MMP-2, expression is consistent with GM3 levels in several B16 cell variants produced by genetic manipulation, while MMP-9 is increased by GM3 addition to these cells and decreased with inhibition of glycolipid synthesis by d-threo-1-phenyl-2-decanoylamino-3- morpholino-1-propanol (D-PDMP). GM3 stimulation of cells enhanced AKT phosphorylation as well as MMP-9 synthesis. LY294002 showed a potent inhibitory effect on MMP-9 synthesis and AKT phosphorylation at Ser 473, either with or without GM3 stimulation, indicating a central role for the PI3K/AKT pathway in this process. An MMP inhibitor, GM6001, clearly inhibited cell motility by suppressing MMP-9 expression and activation. Taken together, these results support the notion that the ganglioside GM3 positively regulates MMP-9 expression (but not MMP-2) and may contribute to murine melanoma metastasis via activation of MMP-9 through the PI3K pathway.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
Pages335-348
Number of pages14
Volume705
DOIs
Publication statusPublished - 2011
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume705
ISSN (Print)00652598

Fingerprint

Experimental Melanomas
Matrix Metalloproteinase 9
Phosphatidylinositol 3-Kinases
Up-Regulation
Tumor Necrosis Factor-alpha
G(M3) Ganglioside
Phosphorylation
Matrix Metalloproteinase 2
Chemical activation
Neoplasm Metastasis
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Oncology
Matrix Metalloproteinase Inhibitors
Polymerase chain reaction
RNA-Directed DNA Polymerase
Glycolipids
Gelatin
Reverse Transcriptase Polymerase Chain Reaction
Cell Movement
Tumors

Keywords

  • Cell motility
  • GM3
  • GM6001
  • Matrix metalloproteinase-9
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wang, P., Wang, X., Wu, P., Zhang, J., Sato, T., Yamagata, S., & Yamagata, T. (2011). GM3 upregulation of matrix metalloproteinase-9 possibly through PI3K, AKT, RICTOR, RHOGDI-2, and TNF-a pathways in mouse melanoma B16 cells. In Advances in Experimental Medicine and Biology (Vol. 705, pp. 335-348). (Advances in Experimental Medicine and Biology; Vol. 705). https://doi.org/10.1007/978-1-4419-7877-6_16

GM3 upregulation of matrix metalloproteinase-9 possibly through PI3K, AKT, RICTOR, RHOGDI-2, and TNF-a pathways in mouse melanoma B16 cells. / Wang, Pu; Wang, Xiaodong; Wu, Peixing; Zhang, Jinghai; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya.

Advances in Experimental Medicine and Biology. Vol. 705 2011. p. 335-348 (Advances in Experimental Medicine and Biology; Vol. 705).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Wang, P, Wang, X, Wu, P, Zhang, J, Sato, T, Yamagata, S & Yamagata, T 2011, GM3 upregulation of matrix metalloproteinase-9 possibly through PI3K, AKT, RICTOR, RHOGDI-2, and TNF-a pathways in mouse melanoma B16 cells. in Advances in Experimental Medicine and Biology. vol. 705, Advances in Experimental Medicine and Biology, vol. 705, pp. 335-348. https://doi.org/10.1007/978-1-4419-7877-6_16
Wang P, Wang X, Wu P, Zhang J, Sato T, Yamagata S et al. GM3 upregulation of matrix metalloproteinase-9 possibly through PI3K, AKT, RICTOR, RHOGDI-2, and TNF-a pathways in mouse melanoma B16 cells. In Advances in Experimental Medicine and Biology. Vol. 705. 2011. p. 335-348. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-1-4419-7877-6_16
Wang, Pu ; Wang, Xiaodong ; Wu, Peixing ; Zhang, Jinghai ; Sato, Toshinori ; Yamagata, Sadako ; Yamagata, Tatsuya. / GM3 upregulation of matrix metalloproteinase-9 possibly through PI3K, AKT, RICTOR, RHOGDI-2, and TNF-a pathways in mouse melanoma B16 cells. Advances in Experimental Medicine and Biology. Vol. 705 2011. pp. 335-348 (Advances in Experimental Medicine and Biology).
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