Nuclear entrapment of p33(ING1b) by inhibition of exportin-1: A trigger of apoptosis in head and neck squamous cell cancer

Abstract

The effect of deregulation of nuclear export mediated by exportin-L with consequent cellular mislocalization of p33(ING1b), a member of the tumor suppressor gene family, has not been previously investigated in head and neck squamous cell cancer (IINSCC). We evaluated the effect of reversing cytoplasmic p33(ING1b) localization through inhibition of exportin-1 by leptomycin B (LMB) and the effect of nuclear entrapment of p33(ING1b) on molecular alterations in primary and metastatic IINSCC lines. The expression and location of exportin-1 and p33(ING1b) We re analyzed by a quantitative real-time reverse transcription polymerase chain reaction PCR (qRT-PCR), a Western blot, and iminunostaining. Cell proliferation and migration assays were conducted to determine the effect of exportin-1 inhibition on the cell lines. Exportin-1 was overexpressed in metastatic FINSCC, whereas p33(ING1) was poorly expressed. Exportin-1 inhibition induced nuclear entrapment and upregulation of p33(ING1b), extensive apoptosis, and growth arrest. It also suppressed cell migration. Cytoplasmic p33(ING1b)-mediated regulation of cell growth and nuclear entrapment of p33(ING1b) via inhibition of exportin-1 may be a key mechanism for inducing IINSCC apoptosis.