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Updated: May 12, 2026

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Published on: October 27, 2020
Effects of TGF-β signaling in clear cell renal cell carcinoma cells
Anna-Karin Boström1, David Lindgren, Martin E Johansson
1Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, Malmö, SE-205 02 Malmö, Sweden.
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.
Insights
Transforming Growth Factor-β (TGF-β) inhibition reduces kidney cancer invasion. This pathway overlaps with hypoxia-inducible factors, suggesting a link between VHL gene function and TGF-β activity in clear cell renal cell carcinoma (ccRCC).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer, often linked to von Hippel-Lindau (VHL) gene loss.
- Metastatic ccRCC has a poor prognosis, with current therapies being insufficient.
- Transforming Growth Factor-β (TGF-β) signaling plays a complex role in tumor progression.
Purpose of the Study:
- To elucidate the role of TGF-β signaling in ccRCC progression.
- To investigate the effects of modulating TGF-β pathway activity in ccRCC cells.
- To identify the relationship between TGF-β and hypoxia-inducible factor (HIF) pathways in ccRCC.
Main Methods:
- Investigated TGF-β pathway modulation effects on ccRCC cell invasion.
- Performed expression profiling to identify TGF-β-induced gene signatures.
- Conducted functional experiments to link TGF-β, HIF, and VHL pathways.
Main Results:
- TGF-β pathway inhibition was shown to significantly attenuate the invasive capacity of ccRCC cells.
- Expression profiling revealed substantial overlap between TGF-β-responsive genes and HIF-regulated genes.
- Functional experiments confirmed that TGF-β pathway activity decreases with the reintroduction of functional VHL.
Conclusions:
- TGF-β signaling is a potential therapeutic target for reducing ccRCC cell invasion.
- A significant crosstalk exists between the TGF-β and hypoxia pathways in ccRCC.
- Restoration of VHL function impacts TGF-β pathway activity, highlighting a VHL-TGF-β axis in ccRCC.
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