title: 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.affiliation: Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, PO Box 29, 103 WenHua Road, Shenyang, LiaoNing 110016, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sato
authors.forename: Sadako
authors.initials: S
authors.lastname: Yamagata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D012516:Osteosarcoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D009025:Morpholines; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C064020:ganglioside GD1alpha; D005677:G(M1) Ganglioside; C033110:RV 538; C061570:protein kinase N; D011493:Protein Kinase C; D020780:Matrix Metalloproteinase 9