NBPF7 promotes the proliferation of α-catenin-knockdown HaCaT cells via functional interaction with the NF-κB pathway

Abstract

Loss of key components that form cell-cell adherens junctions, such as α-catenin, triggers severe epidermal hyperproliferation. However, the underlying molecular mechanisms remain largely unknown. We report here that neuroblastoma breakpoint family (NBPF) genes are upregulated and that NBPF7 specifically promotes cellular proliferation of α-catenin-silenced HaCaT cells through functional linkage with the NF-κB pathway. Genome-wide profiling of HaCaT cells shows that NBPF genes are upregulated following α-catenin knockdown. Data from western blot analyses are consistent with the activation of the NF-κB pathway as well as increased expression of NBPF7 by α-catenin knockdown. Co-immunoprecipitation assays indicate that NBPF7 could be detected in endogenous activated NF-κB immunoprecipitates. Immunoflurence analyses demonstrate that NBPF7 co-localizes with activated NF-κB in the nucleus after α-catenin silencing. Moreover, inhibition of NBPF7 decreases the proliferation of HaCaT cells and abolishes the enhanced proliferation associated with α-catenin knockdown in HaCaT cells. These results indicate that NBPF7 plays a key role in the α-catenin signaling pathway that regulates cell proliferation of keratinocytes. Our findings suggest that the classical NF-κB pathway plays a critical role in cellular proliferation and that NBPF7 is a functional mediator for α-catenin in the regulation of keratinocyte growth.