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Suppression of Tak1 promotes prostate tumorigenesis

Min Wu1, Lihong Shi, Adela Cimic

  • 1Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Cancer Research
|April 3, 2012
PubMed

Insights

Loss of the MAP3K7 gene, encoding TGF-β activated kinase-1 (Tak1), promotes prostate cancer progression. This study validates Tak1 as a tumor suppressor by showing its loss increases cancer cell proliferation and invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer often involves deletion of chromosome 6q15.1, containing the MAP3K7 gene (encoding TGF-β activated kinase-1, Tak1).
  • The tumor suppressor role of Tak1 in prostate cancer is proposed but not fully understood.

Purpose of the Study:

  • To investigate the function of Tak1 in human and murine prostate cancer.
  • To determine if Tak1 loss contributes to prostate cancer development and progression.

Main Methods:

  • Analysis of Tak1 expression in 50 human prostate cancer specimens.
  • Assessment of proliferation, migration, and invasion in murine prostate stem cells and Tak1-deficient cells.
  • Grafting of Tak1-attenuated murine prostate stem cells with fetal urogenital mesenchyme.

Main Results:

  • Tak1 expression decreased with increasing Gleason grade in human prostate cancers.
  • Tak1 loss enhanced proliferation, migration, and invasion in murine prostate cells.
  • Grafts with Tak1-suppressed cells mimicked prostate cancer progression from hyperplasia to invasive carcinoma.
  • Tak1 suppression led to attenuated p38 and c-Jun-N-terminal kinase activity and increased proliferation in grafts.

Conclusions:

  • Findings functionally validate Tak1 as a tumor suppressor in prostate cancer.
  • Loss of Tak1 contributes to prostate cancer progression by increasing cell proliferation and invasion.

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