Cancer and the Nuclear Pore Complex

The nuclear pore complex (NPC) mediates trafficking between the cytoplasm and nucleoplasm. It also plays key roles in other nuclear processes such as chromatin silencing, transcriptional regulation, and DNA damage repair. Nucleoporins, the structural components of the NPC, have been linked to a multitude of cancers through chromosomal translocations generating fusion proteins, changes in protein expression levels, and single point mutations. Only a small number of nucleoporins have been linked to tumorigenesis thus far, and these proteins-Nup62, Nup88, Nup98, Nup214, Nup358/RanBP2, and Tpr-line the trafficking pathway and are particularly associated with mRNA export. Overexpression of several associated nuclear export factors, most also involved in various stages of mRNA export, has been linked to cancers as well. Some oncogenic nucleoporin mutants are mislocalized to either the cytoplasm or nucleoplasm while others are incorporated into the NPC, and in all these cases they are thought to misregulate signaling pathways and transcription through either altered or diminished nucleoporin functionality. Intriguingly, many viruses target the same cancer-linked nucleoporins, often causing their degradation or mislocalization, implying that these viruses exploit some of the same weaknesses as the oncogenic defects.