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The role of the unfolded protein response in tumour development: friend or foe?
Yanjun Ma1, Linda M Hendershot
1Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nature Reviews. Cancer
|December 2, 2004
Summary
Cancer cells face nutrient and oxygen scarcity, activating the unfolded protein response (UPR). While initially protective, prolonged UPR can lead to cancer cell death or altered tumor growth and drug sensitivity.
Area of Science:
- Molecular biology
- Cancer research
- Cellular stress response
Background:
- Cancer cells accumulate mutations enabling survival despite cell-cycle and apoptotic checkpoints.
- Nutrient and oxygen deprivation are critical survival obstacles for cancer cells.
- These stresses impact protein folding in the endoplasmic reticulum, activating the unfolded protein response (UPR).
Purpose of the Study:
- To investigate the role of the unfolded protein response (UPR) in cancer cell survival and progression.
- To explore the UPR's influence on the balance between cancer cell death, dormancy, and aggressive growth.
- To determine how UPR affects solid tumor sensitivity to chemotherapy.
Main Methods:
- Analysis of UPR signaling pathway components.
- Review of clinical studies investigating UPR in cancer patients.
- Examination of the relationship between UPR activation and tumor characteristics.
Main Results:
- The UPR is a cytoprotective pathway activated by endoplasmic reticulum stress.
- Prolonged UPR activation can paradoxically lead to cancer cell apoptosis.
- UPR plays a key role in regulating cancer cell fate and chemosensitivity.
Conclusions:
- The unfolded protein response is a critical regulator of cancer cell survival, dormancy, and growth.
- UPR modulation presents a potential therapeutic strategy for altering solid tumor response to chemotherapy.