Format

Send to

Choose Destination
Semin Cancer Biol. 2014 Aug;27:39-45. doi: 10.1016/j.semcancer.2014.06.003. Epub 2014 Jun 17.

Snail nuclear transport: the gateways regulating epithelial-to-mesenchymal transition?

Author information

1
Department of Oncology, Karmanos Cancer Institute, USA.
2
Department of Oncology, Karmanos Cancer Institute, USA; Division of Research, Hamad Medical Corporation, Doha, Qatar.
3
Department of Pathology, Wayne State University, School of Medicine, Detroit, MI, USA. Electronic address: azmia@karmanos.org.

Abstract

Epithelial-to-mesenchymal transition (EMT) and the reverse process (MET) play central role in organ developmental biology. It is a fine tuned process that when disturbed leads to pathological conditions especially cancers with aggressive and metastatic behavior. Snail is an oncogene that has been well established to be a promoter of EMT through direct repression of epithelial morphology promoter E-cadherin. It can function in the nucleus, in the cytosol and as discovered recently, extracellularly through secretory vesicular structures. The intracellular transport of snail has for long been shown to be regulated by the nuclear pore complex. One of the Karyopherins, importin alpha, mediates snail import, while exportin 1 (Xpo1) also known as chromosome maintenance region 1 (CRM1) is its major nuclear exporter. A number of additional biological regulators are emerging that directly modulate Snail stability by altering its subcellular localization. These observations indicate that targeting the nuclear transport machinery could be an important and as of yet, unexplored avenue for therapeutic intervention against the EMT processes in cancer. In parallel, a number of novel agents that disrupt nuclear transport have recently been discovered and are being explored for their anti-cancer effects in the early clinical settings. Through this review we provide insights on the mechanisms regulating snail subcellular localization and how this impacts EMT. We discuss strategies on how the nuclear transport function can be harnessed to rein in EMT through modulation of snail signaling.

KEYWORDS:

CRM1; EMT; Karyopherin; Nuclear transport; Xpo1

PMID:
24954011
PMCID:
PMC4165636
DOI:
10.1016/j.semcancer.2014.06.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center