Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection
2015
The integrity of eukaryotic cellular function depends on molecular and
biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven
mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three
different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1
(CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed
the available evidence supporting the relevance of CRM1 in the biology of several human neoplasms, its potential role in
drug resistance, and its promise as a therapeutic target. Here we discuss different cancer related proteins (tumor
suppressor genes, oncogenes, and enzymatic therapeutic targets), their function, and their association with CRM1, as well
as agents that specifically inhibit CRM1, their mechanism of action, and their clinical relevance in certain human
neoplasms. The directionality of nuclear transport and the specific molecular cargo in question are of paramount
importance when examining the effects that CRM1 inhibition may have on cellular pathophysiology. The available data
point out the potential role of CRM1-dependent nuclear export of regulatory proteins in the biology of certain human
malignancies. Further studies should expand and clarify the importance of this mechanism in the pathobiology of human
neoplasia.
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