Targeting nucleocytoplasmic transport in cancer therapy

Richard Hill, Bastien Cautain, Nuria De Pedro, Wolfgang Link

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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 specifc 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 signifcant need for novel, specifc 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
Original languageEnglish
Pages (from-to)11-28
Number of pages18
JournalOncotarget
Volume5
Issue number1
Early online date24 Nov 2013
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • tumor suppressors
  • cancer
  • anti-theraphy
  • nuclear export
  • nuclear implant

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