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

Boström, Anna-Karin LU ; Lindgren, David LU ; Johansson, Martin LU and Axelson, Håkan LU (2013) In Biochemical and Biophysical Research Communications 435(1). p.126-133
Abstract
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... (More)
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. (Less)
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publication status
published
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in
Biochemical and Biophysical Research Communications
volume
435
issue
1
pages
126 - 133
publisher
Elsevier
external identifiers
  • wos:000320012900021
  • pmid:23618868
  • scopus:84878186292
  • pmid:23618868
ISSN
1090-2104
DOI
10.1016/j.bbrc.2013.04.054
language
English
LU publication?
yes
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Department affilation moved from v1000583 (Molecular Tumour Biology) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:41:47.
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bd9b74ec-2a39-4309-86c0-896ff22dd80d (old id 3733351)
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http://www.ncbi.nlm.nih.gov/pubmed/23618868?dopt=Abstract
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@article{bd9b74ec-2a39-4309-86c0-896ff22dd80d,
  abstract     = {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.},
  author       = {Boström, Anna-Karin and Lindgren, David and Johansson, Martin and Axelson, Håkan},
  issn         = {1090-2104},
  language     = {eng},
  number       = {1},
  pages        = {126--133},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Effects of TGF-β signaling in Clear Cell Renal Cell Carcinoma cells.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2013.04.054},
  doi          = {10.1016/j.bbrc.2013.04.054},
  volume       = {435},
  year         = {2013},
}