Effects of TGF-β signaling in Clear Cell Renal Cell Carcinoma cells.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3733351
- author
- Boström, Anna-Karin LU ; Lindgren, David LU ; Johansson, Martin LU and Axelson, Håkan LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- additional info
- Department affilation moved from v1000583 (Molecular Tumour Biology) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:41:47.
- id
- bd9b74ec-2a39-4309-86c0-896ff22dd80d (old id 3733351)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23618868?dopt=Abstract
- date added to LUP
- 2016-04-01 10:15:29
- date last changed
- 2022-05-13 07:03:59
@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}}, }