The human Golgi anti-apoptotic protein induces cell invasion by an H 2 O 2 -dependent mechanism

Abstract

The human Golgi anti-apoptotic protein (hGAAP) is a novel highly conserved Golgi-localized cation channel that modulates Ca2+ fluxes from the intracellular stores, inhibits apoptosis and increases cell motility via a SOCE-dependent calpain2 activation that increases focal adhesions turnover. GAAP is expressed in all human tissues and is considered a housekeeping gene. Bioinformatics analyses suggest a link between dysregulation of hGAAP expression and several human cancers. Unpublished data indicate that hGAAP overexpression increases in vitro and in vivo cell invasion, extracellular proteolytic activity and specifically MMP2. Conversely, hGAAP KD by siRNA reduces cell invasion, while the overexpression of an hGAAP null mutant has no effect on cell invasion or proteolytic degradation. Moreover, the overexpression of hGAAP results in an accumulation of intracellular ROS levels (CellROX) and specifically of H2O2 (HyPerRed). The reduction of both hGAAP-induced in vitro cell invasion and extracellular proteolytic degradation upon catalase treatment indicates that H2O2 plays a role in this mechanism. A deeper understanding of hGAAP impact on cell invasion might contribute to provide new insights into the complex mechanisms related to Ca2+ and ROS signaling involved in cell invasion.