Nucleoporins in Cancer: Functional Roles and Therapeutic Opportunities

Abstract

The nuclear pore complex (NPC) and its building-block proteins nucleoporins (NUPs) play fundamental roles in maintaining cellular fitness by regulating nucleocytoplasmic transport, chromatin and transcriptional activity, and genome stability. These core biological processes are critical for cancer cells, and thus tumor-driven co-option of NUP-regulated functions have emerged as important mechanisms contributing to the pathogenesis of multiple malignancies. This review discusses how NUP dysregulation mechanistically contributes to tumor initiation and progression, and how these insights open opportunities for innovative anticancer therapies, including using clinical-grade molecular glues that induce selective NUP degradation and pharmacologically inhibiting NPC-regulated epigenomic/transcriptomic signaling and nucleocytoplasmic transport.