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Updated: Feb 8, 2026
09:14
Tracking Hypoxic Signaling within Encapsulated Cell Aggregates
Published on: December 16, 2011
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Notch signaling promotes a HIF2α-driven hypoxic response in multiple tumor cell types
Anders P Mutvei1, Sebastian K-J Landor1,2, Rhys Fox1
1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Oncogene
|July 12, 2018
Summary
Notch signaling controls the cellular hypoxic response by regulating HIF2α expression. This Notch-driven upregulation of HIF2α may influence cancer progression and offers potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Hyperactivation of Notch signaling and the cellular hypoxic response are common in cancers.
- While hypoxia's effect on Notch is known, Notch's regulation of the hypoxic response is less understood.
Purpose of the Study:
- To investigate whether Notch signaling regulates the cellular hypoxic response.
- To identify the specific mediators involved in this regulation.
Main Methods:
- Analyzing Notch signaling's effect on HIF2α expression in various cancer cell lines under normoxic conditions.
- Utilizing HIF2α siRNA to assess the impact of HIF2α knockdown on Notch-induced gene expression.
- Comparing HIF1α and HIF2α protein levels in response to Notch signaling.
Main Results:
- Notch signaling transcriptionally upregulates HIF2α, leading to elevated HIF2α protein levels in multiple cancer types.
- High Notch signaling can induce a switch from HIF1α to HIF2α dominance.
- HIF2α is essential for approximately 21% of Notch-induced genes, as demonstrated by siRNA knockdown experiments.
Conclusions:
- Notch signaling directly impacts the cellular hypoxic response by controlling HIF2α expression.
- This regulation of HIF2α by Notch signaling presents a potential target for novel cancer therapies.
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