Title: Regulation of tumor metastasis by ganglioside GD1a in mouse osteosarcoma FBJ cells: NOS2 is regulated by GD1a through GRB2/MEK2/ERK1 but not EGFR

Presenter: Prof. Tatsuya Yamagata

University: Laboratory of Tumor Biology and Glycobiology, Dept. of Life Sciences, Shenyang Pharmaceutical University

Time: 9:30-10:30, 15 April, 2011

Venue: A203, Institute of Microbiology, Chinese Academy of Sciences

Abstract: We are interested in the ganglioside regulation of tumor metastasis and the underlying mechanism by which ganglioside regulates cell behaviors. Murine osteosarcoma FBJ-S1 cells have poor metastatic properties, but the variant FBJ-LL cells are highly metastatic (1, 2). Expression of the ganglioside GM3 was equivalent in FBJ-LL and FBJ-S1 cells, but GD1a expression was much higher in FBJ-S1 cells than in the highly metastatic FBJ-LL cells (3). GD1a was found to be a main factor in the regulation of cell metastasis and cell motility (4). GD1a increased the expression of caveolin-1 and stromal interaction molecule 1 (Stim1) (5), decreased the expression of TNFα (6), MMP-9 (7), and NOS2 (8), HGF (9) and suppressed the phosphorylation of the hepatocyte growth factor receptor, c-MET (10). RNA silencing of NOS2 in FBJ-LL cells caused inhibition of cell metastatic properties; cell motility was suppressed in wound healing and Transwell migration assays, and growth was retarded in soft agar cultivation (anchorage independent growth) of FBJ-LL cells. We have recently shown (8, 11) that NOS2 suppression in quiescent or EGF-stimulated cells was mediated through EGFR/GRB2/MEK2/ERK1; however, a GD1a signal mediated by GRB2/MEK2/ERK1 could also suppress NOS2 without the involvement of EGFR.