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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
PTRF/cavin-1 is essential for multidrug resistance in cancer cells
Jae-Sung Yi1, Dong-Gi Mun, Hyun Lee
1Division of Life Sciences, College of Life Sciences and Biotechnology, Research Institute for Natural Sciences, Korea University, Seoul, 136-701, South Korea, and.
Abstract:
Since detergent-resistant lipid rafts play important roles in multidrug resistance (MDR), their comprehensive proteomics could provide new insights to understand the underlying molecular mechanism of MDR in cancer cells. In the present work, lipid rafts were isolated from MCF-7 and adriamycin-resistant MCF-7/ADR cells and their proteomes were analyzed by label-free quantitative proteomics. Polymerase I and transcript release factor (PTRF)/cavin-1 was measured to be upregulated along with multidrug-resistant P-glycoprotein, caveolin-1, and serum deprivation protein response/cavin-2 in the lipid rafts of MCF-7/ADR cells. PTRF knockdown led to reduction in the amount of lipid rafts on the surface of MCF7/ADR cells as determined by cellular staining with lipid raft-specific dyes such as S-laurdan2 and FITC-conjugated cholera toxin B. PTRF knockdown also reduced MDR in MCF-7/ADR cells. These data indicate that PTRF is necessary for MDR in cancer cells via the fortification of lipid rafts.
Insights
Polymerase I and transcript release factor (PTRF) is crucial for multidrug resistance (MDR) in cancer cells. This protein strengthens lipid rafts, enhancing MDR by fortifying these structures.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Detergent-resistant lipid rafts are implicated in multidrug resistance (MDR) in cancer.
- Understanding the proteomic composition of lipid rafts is key to elucidating MDR mechanisms.
Purpose of the Study:
- To investigate the proteomic differences in lipid rafts between sensitive and resistant cancer cells.
- To identify key proteins involved in MDR within lipid rafts.
Main Methods:
- Isolation of lipid rafts from MCF-7 and adriamycin-resistant MCF-7/ADR cells.
- Label-free quantitative proteomics to analyze lipid raft proteomes.
- PTRF knockdown and assessment of lipid raft quantity and MDR.
Main Results:
- Polymerase I and transcript release factor (PTRF)/cavin-1 was upregulated in resistant MCF-7/ADR cells.
- PTRF knockdown reduced lipid raft abundance and decreased MDR in MCF-7/ADR cells.
- PTRF is associated with P-glycoprotein and caveolin-1 in lipid rafts of resistant cells.
Conclusions:
- PTRF plays a critical role in establishing and maintaining multidrug resistance in cancer cells.
- PTRF fortifies lipid rafts, thereby contributing to the MDR phenotype.
- PTRF is a potential therapeutic target for overcoming MDR in cancer.
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