Regenerating islet-derived family member, 4 modulates multiple receptor @entity669 kinases and mediators of drug resistance in XXXX .

@entity10642 @entity588 @entity14511 @entity5 @entity470 @entity993 @entity3544 @entity2284 @entity584 @entity669 @entity4357
Regenerating islet-derived family member, 4 ( @entity14511 ) is a secreted protein and member of the C-type lectin superfamily. Expression analyses have characterized @entity14511 as a prognostic marker for certain @entity5 ; however, the functional role of @entity14511 in @entity5 , including downstream signaling, has only begun to be elucidated. To investigate the biological role of @entity14511 in @entity5 , phosphorylation events were studied in @entity5 cell lines in the context of either @entity14511 stimulation (HCT116 cells) or knockdown of endogenous @entity14511 ( @entity10642 and KM12 cells). In addition to the previously observed impact on @entity470 and @entity584 phosphorylation, we observed modulation in the phosphorylation of multiple additional receptor @entity669 kinases (RTKs), including insulin receptor, insulin-like growth factor receptor as well as their downstream effectors, mitogen-activated protein kinase and @entity4357 -3-kinase pathways. Furthermore, knockdown of @entity14511 impacted the ability of insulin and EGF to stimulate downstream @entity669 phosphorylation. Knockdown of @entity14511 in @entity5 cell lines inhibited anchorage-dependent and anchorage-independent (both soft-agar and spheroid assays) cell growth and induced cell cycle arrest. This was accompanied by upregulation of @entity3544 and @entity993 . Transiently silencing @entity14511 in @entity5 cells induced apoptosis and downregulated @entity588 . Conversely, stimulation of HCT116 cells with recombinant @entity14511 induced @entity588 . @entity2284 , a molecule implicated in drug resistance, was similarly modulated by @entity14511 . Consistent with our observations with @entity14511 siRNA-mediated knockdown, monoclonal antibodies directed against @entity14511 inhibited @entity10642 and KM12 cell growth. Collectively, @entity14511 plays an important role in @entity5 by modulation of key signaling molecules including @entity2284 , @entity588 and multiple RTKs.
