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

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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.

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  • Biological Sciences
Original languageEnglish
Pages (from-to)126-133
JournalBiochemical and Biophysical Research Communications
Volume435
Issue number1
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Department affilation moved from v1000583 (Molecular Tumour Biology) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:41:47.