Oncotarget

Reviews:

Targeting nucleocytoplasmic transport in cancer therapy

Richard Hill _, Bastien Cautain, Nuria de Pedro and Wolfgang Link

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Oncotarget. 2014; 5:11-28. https://doi.org/10.18632/oncotarget.1457

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Abstract

Richard Hill1,2,*, Bastien Cautain3,*, Nuria de Pedro3 and Wolfgang Link1,2,*

1 Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Portugal

2 IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Campus de Gambelas, Faro, Portugal

3 Fundacion MEDINA Parque tecnológico ciencias de la salud, Avd. Conocimiento 3, Granada, Spain

* These authors contributed equally to this work.

Correspondence:

Wolfgang Link, email:

Keywords: Tumor suppressors, Cancer, Anti-cancer therapy, Nuclear export, nuclear import

Received: September 30, 2013 Accepted: November 22, 2013 Published: November 24, 2013

Abstract

The intracellular location and regulation of proteins within each cell is critically important and is typically deregulated in disease especially cancer. The clinical hypothesis for inhibiting the nucleo-cytoplasmic transport is based on the dependence of certain key proteins within malignant cells. This includes a host of well-characterized tumor suppressor and oncoproteins that require specific localization for their function. This aberrant localization of tumour suppressors and oncoproteins results in their their respective inactivation or over-activation. This incorrect localization occurs actively via the nuclear pore complex that spans the nuclear envelope and is mediated by transport receptors. Accordingly, given the significant need for novel, specific disease treatments, the nuclear envelope and the nuclear transport machinery have emerged as a rational therapeutic target in oncology to restore physiological nucleus/cytoplasmic homeostasis. Recent evidence suggests that this approach might be of substantial therapeutic use. This review summarizes the mechanisms of nucleo-cytoplasmic transport, its role in cancer biology and the therapeutic potential of targeting this critical cellular process


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