Related Experiment Video
Updated: Jul 5, 2025

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
Published on: May 12, 2017
Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein
Nan Lin1,2, Liankun Sun2, Jiannan Chai3
1First Hospital of Jilin University, Changchun, China.
Abstract:
Drug resistance remains a challenge in ovarian cancer. In addition to aberrant activation of relevant signaling pathways, the adaptive stress response is emerging as a new spotlight of drug resistance in cancer cells. Stress granules (SGs) are one of the most important features of the adaptive stress response, and there is increasing evidence that SGs promote drug resistance in cancer cells. In the present study, we compared two types of ovarian cancer cells, A2780 and SKOV3, using the dual PI3K/mTOR inhibitor, PKI-402. We found that SGs were formed and SGs could intercept the signaling factor ATF5 and regulate the mitochondrial unfolded protein response (UPRmt) in A2780 cells. Therefore, exploring the network formed between SGs and membrane-bound organelles, such as mitochondria, which may provide a new insight into the mechanisms of antitumor drug functions.
Insights
Stress granules (SGs) contribute to drug resistance in ovarian cancer by intercepting ATF5 and regulating mitochondrial responses. Targeting SGs may offer new strategies against drug-resistant ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Stress Response
Background:
- Drug resistance is a major obstacle in ovarian cancer treatment.
- The adaptive stress response, particularly stress granules (SGs), is increasingly recognized as a key mechanism in cancer drug resistance.
Purpose of the Study:
- To investigate the role of stress granules (SGs) in mediating drug resistance in ovarian cancer cells.
- To explore the interaction between SGs, signaling factors, and organelle responses under drug treatment.
Main Methods:
- Utilized A2780 and SKOV3 ovarian cancer cell lines.
- Treated cells with the dual PI3K/mTOR inhibitor PKI-402.
- Analyzed the formation of stress granules and their interaction with ATF5 and the mitochondrial unfolded protein response (UPRmt).
Main Results:
- PKI-402 induced stress granule formation in A2780 ovarian cancer cells.
- Stress granules were found to intercept the signaling factor ATF5.
- Stress granule formation was linked to the regulation of the mitochondrial unfolded protein response (UPRmt).
Conclusions:
- Stress granules play a significant role in the adaptive stress response contributing to drug resistance in ovarian cancer.
- The interaction between stress granules and signaling pathways like ATF5, and organelle responses like UPRmt, is crucial for understanding drug resistance.
- Investigating the network of SGs and membrane-bound organelles offers novel insights into antitumor drug mechanisms.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Regulation of the Unfolded Protein Response
The Unfolded Protein Response
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades

