Karyopherins in cancer

Abstract

Malfunction of nuclear-cytoplasmic transport contributes to many diseases including cancer. Defective nuclear transport leads to changes in both the physiological levels and temporal-spatial location of tumor suppressors, proto-oncogenes and other macromolecules that in turn affect the tumorigenesis process and drug sensitivity of cancer cells. In addition to their nuclear transport functions in interphase, Karyopherin nuclear transport receptors also have important roles in mitosis and chromosomal integrity. Therefore, alterations in the expressions or regular functions of Karyopherins may have substantial effects on the course and outcome of diseases.

Figure 1. Kap-mediated nuclear import and export

Nuclear import and export of macromolecules occur through the nuclear pore complex (NPC) and are mediated by the Karyopherin family of nuclear transport receptors. Kap-mediated nuclear transport is regulated by the small GTPase Ran, which controls assembly and disassembly of Kap-cargo complexes. The Importins Impβ and Kapβ2 are in cyan, the adaptor protein Impα is in red and the Exportins CRM1/XPO1 and CAS are in blue and dark blue, respectively.

Figure 2. Kap-mediated nuclear transport systems and their impact on the hallmarks of cancer

The ten hallmarks of cancer are shown with associated Kaps that were reported to be involved in cancer onset and progression. The cancer hallmarks diagram is adapted from [20].