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Akt inhibitor a-443654 interferes with mitotic progression by regulating aurora a kinase expression

Xuesong Liu1, Yan Shi, Keith W Woods

  • 1Department of R47S, GPRD, Abbott Laboratories, Abbott Park, IL 60064, USA. xuesong.liu@abbott.com

Neoplasia (New York, N.Y.)
|August 2, 2008
PubMed

Insights

Akt inhibitors, like Compound A, disrupt cell division by affecting spindle formation. Akt signaling promotes mitotic progression by transcriptionally upregulating Aurora A kinase.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Akt and Aurora A kinase are critical targets in cancer therapy.
  • Akt signaling pathways are frequently dysregulated in various cancers.

Purpose of the Study:

  • To investigate the role of Akt in mitotic progression and its relationship with Aurora A kinase.
  • To elucidate the mechanism by which Akt inhibitors affect cell division.

Main Methods:

  • Utilized Compound A, a specific Akt inhibitor, and LY294002, a PI3K inhibitor.
  • Performed gene expression array studies and analyzed Aurora A promoter activity.
  • Investigated the effect of Aurora A overexpression in cells treated with Compound A.

Main Results:

  • Compound A induced G(2)/M cell cycle arrest, disrupted spindle formation, and inhibited Aurora A promoter activity.
  • Akt pathway inhibition, but not mTOR inhibition, reduced Aurora A transcription.
  • Overexpression of Aurora A rescued the mitotic defects caused by Akt inhibition.

Conclusions:

  • Akt signaling promotes mitotic progression, at least in part, through the transcriptional regulation of Aurora A.
  • Targeting the Akt/Aurora A pathway presents a potential therapeutic strategy for cancer treatment.

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