>>17-aag also synergizes with taxol, Keryx' UCN-01, and some Lilly drug I forget (and there may be others)<<
>>Mol Cancer Res. 2006 Nov;4(11):873-83.
MUC1 Oncoprotein Functions in Activation of Fibroblast Growth Factor Receptor Signaling.
Ren J, Raina D, Chen W, Li G, Huang L, Kufe D.
Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. donald_kufe@dfci.harvard.edu.
Activation of the fibroblast growth factor (FGF) receptor 3 (FGFR3) has been linked to the development of human cancers by mechanisms that are not well understood. The MUC1 oncoprotein is aberrantly overexpressed by certain hematologic malignancies and most human carcinomas. The present studies show that MUC1 associates with FGFR3. Stimulation of cells with FGF1 increased the interaction between MUC1 and FGFR3. FGF1 stimulation also induced c-Src-dependent tyrosine phosphorylation of the MUC1 cytoplasmic domain on a YEKV motif. FGF1-induced tyrosine phosphorylation of MUC1 was associated with increased binding of MUC1 to beta-catenin and targeting of MUC1 and beta-catenin to the nucleus. FGF1 also induced binding of MUC1 to the heat shock protein 90 (HSP90) chaperone by a mechanism dependent on phosphorylation of the YEKV motif. Notably, beta-catenin and HSP90 compete for binding to the MUC1 cytoplasmic domain, indicating that MUC1 forms mutually exclusive complexes with these proteins. The results also show that inhibition of HSP90 with geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin attenuates FGF1-induced binding of MUC1 to HSP90 and targeting of MUC1 to the mitochondrial outer membrane. These findings indicate that FGF1 induces phosphorylation of MUC1 on YEKV and thereby activates two distinct pathways: (a) nuclear localization of MUC1 and beta-catenin and (b) delivery of MUC1 to mitochondria by HSP90.<<
Genzyme munched ILEX, which was working on MUC1 as a target, so Genzyme is a possible partner/suitor, too. More likely a partner in a minor collaboration or licensing agreement, since GENZ must know digest AnorMED. There might be other commercial programs, but I didn't find 'em with a quick search.
Cheers, Tuck |
