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Efficient induction of apoptosis by wee1 kinase inhibition in hepatocellular carcinoma cells

Tomomi Kogiso1, Hikaru Nagahara2, Etsuko Hashimoto1

  • 1Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Plos One
|June 25, 2014
PubMed

Insights

Transforming growth factor-β1 (TGF-β1) inhibits hepatocellular carcinoma (HCC) cell growth by reducing Wee1 kinase. Wee1 kinase inhibitors show promise for treating advanced HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Transforming growth factor-β1 (TGF-β1) is a potent inhibitor of human hepatocellular carcinoma (HCC) cell proliferation.
  • The precise molecular mechanisms underlying TGF-β1's anti-proliferative effects in HCC require further elucidation.

Purpose of the Study:

  • To investigate the role of Wee1 kinase in TGF-β1-induced apoptosis of HCC cells.
  • To evaluate the therapeutic potential of targeting Wee1 kinase in advanced HCC.

Main Methods:

  • Investigated the effect of TGF-β1 on cdc2 phosphorylation and Wee1 kinase expression in HCC cells.
  • Utilized a Wee1 kinase inhibitor to induce apoptosis in HCC cells.
  • Analyzed Wee1 kinase expression in surgically resected HCC and non-cancerous tissues.

Main Results:

  • TGF-β1 treatment led to decreased phosphorylation of cdc2 at Tyr15 and down-regulation of Wee1 kinase expression.
  • A Wee1 kinase inhibitor effectively induced apoptosis in HCC cells, independent of TGF-β1.
  • Wee1 kinase was significantly expressed in moderately to poorly differentiated HCC tissues but not in non-cancerous or cirrhotic tissues.

Conclusions:

  • TGF-β1-induced apoptosis in HCC is mediated by the down-regulation of Wee1 kinase and subsequent decreased cdc2 phosphorylation.
  • Wee1 kinase represents a potential therapeutic target for advanced HCC.
  • Wee1 kinase inhibitors may offer a novel treatment strategy for advanced hepatocellular carcinoma.

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