4.7 Article

PTRF/Cavin-1 is Essential for Multidrug Resistance in Cancer Cells

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 12, Issue 2, Pages 605-614

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/pr300651m

Keywords

lipid rafts; label-free quantitative proteomics; PTRF; cavin-1; multidrug resistance

Funding

  1. Basic Research Laboratory Program of the Korea Research Foundation [0001197]
  2. National R&D Program for Cancer Control
  3. Ministry of Health, Welfare and Family Affairs [09201800]
  4. Proteogenomic Research Program through the National Research Foundation of Korea
  5. National Project for Personalized Genomic Medicine from Korean Ministry of Health and Welfare [A111218-11-CP02]

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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.

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