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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
Published on: August 2, 2018
Interplay between receptor tyrosine kinases and hypoxia signaling in cancer
Astrid A Glück1, Daniel M Aebersold1, Yitzhak Zimmer1
1Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, Switzerland; Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, Switzerland.
Abstract:
Deregulated signaling via receptor tyrosine kinase (RTK) pathways is prevalent in numerous types of human cancers and is commonly correlated with worst prognosis, resistance to various treatment modalities and increased mortality. Likewise, hypoxic tumors are often manifested by aggressive mode of growth and progression following an adaptive genetic reprogramming with consequent transcriptional activation of genes encoding proteins, which support tumor survival under low oxygen-related conditions. Consequently, both the hypoxia-inducible factor (HIF) system, which is the major mediator of hypoxia-related signaling, and numerous RTK systems are considered critical molecular targets in current cancer therapy. It is now evident that there is an intricate molecular crosstalk between RTKs and hypoxia-related signaling in the sense that hypoxia can activate expression of particular RTKs and/or their corresponding ligands, while some RTK systems have been shown to trigger activation of the HIF machinery. Moreover, signaling regulation of some RTK systems under hypoxic conditions has also been documented to take place in a HIF-independent manner. With this review we aim at overviewing the most current observations on that topic and highlight the importance of the potential co-drugging the HIF system along with particular relevant RTKs for better tumor growth control.
Insights
Receptor tyrosine kinase (RTK) and hypoxia-inducible factor (HIF) signaling are key in cancer. Understanding their crosstalk is crucial for developing new therapies targeting both RTK and HIF pathways for improved tumor control.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling Pathways
Background:
- Deregulated receptor tyrosine kinase (RTK) signaling is common in human cancers, linked to poor prognosis and treatment resistance.
- Hypoxic tumors exhibit aggressive growth and survival through hypoxia-inducible factor (HIF) pathway activation.
- Both RTK and HIF pathways are critical molecular targets in cancer therapy.
Purpose of the Study:
- To review current understanding of the molecular crosstalk between RTKs and hypoxia-related signaling.
- To highlight the significance of targeting these interconnected pathways in cancer treatment.
Main Methods:
- Literature review of current research on RTK and HIF signaling in cancer.
- Analysis of molecular mechanisms underlying the crosstalk between these pathways.
- Evaluation of therapeutic strategies involving co-targeting RTKs and HIF.
Main Results:
- Hypoxia can activate specific RTKs and/or their ligands, while some RTKs activate the HIF machinery.
- RTK signaling can be regulated under hypoxia independently of HIF.
- Complex interplay exists between RTK and hypoxia-induced signaling.
Conclusions:
- The intricate crosstalk between RTK and HIF signaling pathways presents a promising therapeutic avenue.
- Co-drugging specific RTKs alongside the HIF system may offer enhanced tumor growth control.
- Further research into these interactions is vital for advancing cancer therapy.
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