Inhibitor of Growth 4 Suppresses Cell Spreading and Cell Migration by Interacting with a Novel Binding Partner, Liprin alpha 1

Inhibitor of growth 4 (ING4) is a candidate tumor suppressor that plays a major role in gene regulation, cell cycle control, apoptosis, and angiogenesis. ING4 expression is down-regulated in glioblastoma cells and head and neck squamous cell carcinoma. Here, we identified liprin alpha 1/PPFIA1, a cytoplasmic protein necessary for focal adhesion formation and axon guidance, as a novel interacting protein with ING4. ING4 and liprin alpha 1 colocalized at lamellipodia in the vicinity of vinculin. Overexpressed ING4 suppressed cell spreading and cell migration. In contrast, overexpressed liprin alpha 1 enhanced cell spreading and cell migration. Knockdown of endogenous ING4 with RNA interference induced cell motility, whereas knockdown of endogenous liprin alpha 1 suppressed cell motility. ING4 also suppressed cell motility that was enhanced by liprin alpha 1. However, ING4 did not further suppress cell motility when liprin alpha 1 was suppressed with RNA interference, suggesting a functional and mechanistic interdependence between these proteins. In addition to its nuclear functions, cytoplasmic ING4 interacts with liprin alpha 1 to regulate cell migration and, with its known antiangiogenic function, may prevent invasion and metastasis. [Cancer Res 2007; 67(6):2552-8]