GIPC mediates the generation of reactive oxygen species and the regulation of cancer cell proliferation by insulin-like growth factor-1/IGF-1R signaling

Abstract 

Insulin-like growth factor-1 (IGF-1)/IGF-1 receptor signaling participates in a variety of cellular processes, including cell survival, growth, and proliferation. Increased expression of IGF-1R and activation of its downstream signaling components have been implicated in human cancers. Although a regulatory role for IGF-1R has been established, the relationship between IGF-1R and its binding partner, GAIP-interacting protein C-terminus (GIPC), in terms of promoting cell proliferation, remains unclear. We found that siRNA-mediated silencing of GIPC expression decreased IGF-1-mediated IGF-1R phosphorylation and cellular proliferation in breast cancer models. IGF-1-mediated cellular proliferation was also inhibited by N-acetylcysteine, which implicates reactive oxygen species generation. siRNA-mediated silencing of GIPC expression also decreased IGF-1-mediated reactive oxygen species generation. Taken together, these data suggest that GIPC contributes to IGF-1-induced cancer cell proliferation via the regulation of reactive oxygen species production.

Keywords: IGF-1 signaling, GIPC, PI3-kinase/Akt, Reactive oxygen species, Growth regulation