Ganglioside GD1a suppresses TNFalpha expression via Pkn1 at the transcriptional level in mouse osteosarcoma-derived FBJ cells.

Abstract

Ganglioside GD1a has been reported to suppress metastasis [S. Hyuga, S. Yamagata, Y. Takatsu, M. Hyuga, H. Nakanishi, K. Furukawa, T. Yamagata, Suppression of FBJ-LL cell adhesion to vitronectin by ganglioside GD1a and loss of metastatic capacity, International J. Cancer. 83 (1999) 685-691.] and MMP-9 production in mouse osteosarcoma FBJ cells [D. Hu, Z. Man, P. Wang, X. Tan, X. Wang, S. Takaku, S. Hyuga, T. Sato, X. Yao, S. Yamagata, T. Yamagata, Ganglioside GD1a negatively regulates MMP9 expression in mouse FBJ cell lines at the transcriptional level, Connect. Tissue Res. 48 (2007) 198-205.]. In the present study, TNFalpha increased cell motility and MMP-9 and TNFalpha expression at the transcriptional level. TNFalpha expression was found to be inversely proportional to GD1a content in the FBJ-cell variants. The addition of exogenous GD1a to FBJ-LL cells suppressed TNFalpha expression, and treatment of FBJ-S1 cells with D-PDMP (glucosylceramide synthesis inhibitor) led to an increase in TNFalpha, indicating that TNFalpha is negatively regulated by GD1a in FBJ cells. SiRNA of Pkn1, a Rho-GTPase effecter protein kinase, suppressed TNFalpha levels as well as Pkn1 expression, suggesting that Pkn1 is involved in TNFalpha signaling. Treatment of Pkn1-silenced FBJ-LL cells with GD1a failed to suppress TNFalpha expression, demonstrating that GD1a signals that lead to TNFalpha suppression are transduced through Pkn1.

• Authors: Li Wang, Yinan Wang, Toshinori Sato, Sadako Yamagata, Tatsuya Yamagata
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 371 Issue 2 Pg. 230-5 (Jun 27 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18435913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Morpholines
• RNA, Small Interfering
• Tumor Necrosis Factor-alpha
• ganglioside GD1alpha
• G(M1) Ganglioside
• RV 538
• protein kinase N
• Protein Kinase C
• Matrix Metalloproteinase 9

Topics

• Animals
• Bone Neoplasms (enzymology, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Down-Regulation
• G(M1) Ganglioside (analogs & derivatives, metabolism)
• Gene Expression Regulation, Neoplastic
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Morpholines (pharmacology)
• Osteosarcoma (enzymology, metabolism, pathology)
• Protein Kinase C (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Transcription, Genetic
• Tumor Necrosis Factor-alpha (genetics, metabolism)