TY - JOUR
T1 - Ganglioside GD1a suppresses TNFα expression via Pkn1 at the transcriptional level in mouse osteosarcoma-derived FBJ cells
AU - Wang, Li
AU - Wang, Yinan
AU - Sato, Toshinori
AU - Yamagata, Sadako
AU - Yamagata, Tatsuya
N1 - Funding Information:
This work was in part supported by a fund from Mizutani Foundation for Glycoscience (to T.Y.).
PY - 2008/6/27
Y1 - 2008/6/27
N2 - 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, TNFα increased cell motility and MMP-9 and TNFα expression at the transcriptional level. TNFα 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 TNFα expression, and treatment of FBJ-S1 cells with D-PDMP (glucosylceramide synthesis inhibitor) led to an increase in TNFα, indicating that TNFα is negatively regulated by GD1a in FBJ cells. SiRNA of Pkn1, a Rho-GTPase effecter protein kinase, suppressed TNFα levels as well as Pkn1 expression, suggesting that Pkn1 is involved in TNFα signaling. Treatment of Pkn1-silenced FBJ-LL cells with GD1a failed to suppress TNFα expression, demonstrating that GD1a signals that lead to TNFα suppression are transduced through Pkn1.
AB - 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, TNFα increased cell motility and MMP-9 and TNFα expression at the transcriptional level. TNFα 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 TNFα expression, and treatment of FBJ-S1 cells with D-PDMP (glucosylceramide synthesis inhibitor) led to an increase in TNFα, indicating that TNFα is negatively regulated by GD1a in FBJ cells. SiRNA of Pkn1, a Rho-GTPase effecter protein kinase, suppressed TNFα levels as well as Pkn1 expression, suggesting that Pkn1 is involved in TNFα signaling. Treatment of Pkn1-silenced FBJ-LL cells with GD1a failed to suppress TNFα expression, demonstrating that GD1a signals that lead to TNFα suppression are transduced through Pkn1.
KW - Cell motility
KW - GD1a
KW - Ganglioside
KW - MMP-9
KW - Pkn1
KW - TNFα
KW - siRNA
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U2 - 10.1016/j.bbrc.2008.04.053
DO - 10.1016/j.bbrc.2008.04.053
M3 - Article
C2 - 18435913
AN - SCOPUS:43149112292
SN - 0006-291X
VL - 371
SP - 230
EP - 235
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
