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Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
06:29

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

Oncogenic role of nuclear accumulated Aurora-A

Masaaki Tatsuka1, Sunao Sato, Akifumi Kanda

  • 1Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023, Japan.

Molecular Carcinogenesis
|February 11, 2009
PubMed

Insights

Nuclear accumulation of Aurora-A kinase is crucial for cancer transformation. This finding reveals a new nuclear function for Aurora-A in cancer, suggesting nuclear targets for therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Aurora-A kinase (Aik, BTAK, STK15) is a proto-oncogene overexpressed in many human cancers.
  • Mechanisms of Aurora-A overexpression include gene amplification, mRNA overexpression, and proteolytic resistance.
  • The role of Aurora-A overexpression in cancer cell transformation remains incompletely understood.

Purpose of the Study:

  • To investigate the role of Aurora-A localization in cancer cell transformation.
  • To determine the functional significance of nuclear versus centrosomal Aurora-A.
  • To identify novel therapeutic targets based on Aurora-A function in cancer.

Main Methods:

  • Cellular protein fractionation and immunoblot analysis to determine Aurora-A subcellular localization.
  • Indirect immunofluorescence using confocal laser microscopy to visualize Aurora-A in cancer cells and normal keratinocytes.
  • Functional assays involving expression of nuclear export signal-fused Aurora-A to assess transformation activity.

Main Results:

  • Nuclear accumulation of Aurora-A was observed in head and neck cancer cells, distinct from centrosomal localization in normal oral keratinocytes.
  • Disruption of nuclear localization by a nuclear export signal abolished Aurora-A's oncogenic transformation activity.
  • Previous findings of cytoplasmic Aurora-A via immunohistochemistry may not reflect its functional localization in intact cancer cells.

Conclusions:

  • Nuclear localization of Aurora-A is critical for its oncogenic transformation activity.
  • This study identifies a novel nuclear function of Aurora-A in cancer.
  • Substrates of nuclear Aurora-A represent potential novel therapeutic targets for cancer treatment.

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