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Effects of TGF-β signaling in Clear Cell Renal Cell Carcinoma cells.

Author:
  • Anna-Karin Boström
  • David Lindgren
  • Martin Johansson
  • Håkan Axelson
Publishing year: 2013
Language: English
Pages: 126-133
Publication/Series: Biochemical and Biophysical Research Communications
Volume: 435
Issue: 1
Document type: Journal article
Publisher: Elsevier

Abstract english

Clear cell renal cell carcinoma (ccRCC) is by far the most common type of kidney cancer and is characterized by loss of the tumor suppressor gene von Hippel-Lindau (VHL). ccRCC patients with metastatic disease has poor prognosis and today's therapy is insufficient. The cytokine Transforming Growth Factor-β (TGF-β) has been extensively studied in tumor biology and is believed to serve a variety of functions in tumor progression. We have previously shown that inhibition of NOTCH signaling causes a reduced migratory and invasive capacity of ccRCC cells, at least partly by a cross-talk with the TGF-β pathway. In the present study we aimed to further clarify the role of TGF-β signaling in ccRCC. We investigated the effects of TGF-β pathway modulation and showed that TGF-β inhibition attenuates the invasive capacity of ccRCC cells. By performing expression profiling we obtained a gene signature of the TGF-β induced response in ccRCC cells. The expression analyses revealed an extensive overlap between the TGF-β response and genes regulated by the hypoxia inducible factor (HIF). The link between the hypoxic and the TGF-β pathways was further corroborated by functional experiments, which demonstrated that TGF-β pathway activity was attenuated upon reintroduction of functional VHL in ccRCC.

Keywords

  • Biological Sciences

Other

Published
  • Pathology, Malmö
  • ISSN: 1090-2104
Håkan Axelson
E-mail: hakan [dot] axelson [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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