By behaving as molecular hubs, scaffold
proteins can assemble a large number of signaling molecules and organize complicated intracellular signaling networks in time and space. Owing to their crucial role in mediating intracellular signaling related to
tumor cell growth and migration, recent studies have highlighted the relevance of scaffold
proteins in human
cancers and indicated that interfering with their expression and/or their ability to bind effector
proteins can inhibit
cancer progression. Here, we show that
receptor for activated C-kinase 1 (RACK1), a ubiquitously expressed scaffolding
protein, plays a crucial regulatory role in
tumor growth. Using an RNA silencing approach, we found that downregulation of RACK1 expression in HeLa and A673
tumor cells markedly suppressed the proliferation and invasion of these cells in vitro and
tumor development in vivo. Consequently, we found that significant suppression of constitutive phosphorylation of Akt and MAPK by RACK1 silencing may contribute to the inhibition of
tumor growth. Moreover, RACK1 silencing significantly attenuated
tumor-associated angiogenesis by, at least in part, inhibiting the expression of two critical angiogenic factors, namely
vascular endothelial growth factor-B and
fibroblast growth factor 2. The results of the present study show that RACK1 is a potent enhancer of
tumor growth and, thus, a potential anti-
cancer therapeutic target.