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Status |
Public on Aug 08, 2021 |
Title |
Mitochondrial BCRP sustains the proliferation and survival of drug-resistant breast-cancer cells by regulating intracellular ROS |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
ATP-binding cassette (ABC) transporter family are major contributors to the drug-resistance establishment of breast cancer cells. Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. However, recent studies suggest that the biological function of BCRP is not limited in its drug-pump activity. Herein, the role of BCRP in the proliferation and survival of drug-resistant breast cancer cells was investigated. We found that BCRP is not the major drug pump to efflux epirubicin in the resistant cells that express multiple ABC transporters. Silencing of BCRP significantly impairs cell proliferation and induces apoptosis of the resistant cells in vitro and in vivo. RNA-sequencing and high-throughput proteomics suggest that BCRP is an inhibitory factor of oxidative phosphorylation (OXPHOS). Further research suggests that BCRP is localized in the mitochondria of the resistant cells. Knockdown of BCRP elevated the intracellular reactive oxygen species (ROS) level and eventually promotes the cell to undergo apoptosis. This study demonstrated that BCRP exerts important onco-promoting functions in the drug-resistant breast cancer cells independent of its well-recognized drug-efflux activity, which shed new light on understanding the complex functional role of ABC transporters in drug-resistant cells.
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Overall design |
For transcriptome RNA sequencing (RNA-Seq), SK/EPI, SK-BR-3, SK/EPI-siBCRP and SK/EPI-siNC cells were prepared in triplicates and lysed by Trizol reagent (Invitrogen). Then the cell lysates were processed and sequence by NovoGene (Beijing, China).
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Contributor(s) |
Zhang H, Han X, Wang Z, Wang Z, Cui Y, Tian R, Zhu Y, Han B, Liu H, Zuo X, Ren S, Tian J, Niu R, Zhang F |
Citation(s) |
34650973 |
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Submission date |
Aug 07, 2021 |
Last update date |
Oct 19, 2021 |
Contact name |
He Zhang |
E-mail(s) |
zhanghe1992@tmu.edu.cn
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Phone |
+861360204722
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Organization name |
Tianjin Medical University Cancer Institute and Hospital
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Department |
Public Laboratory
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Street address |
Tianjin 300060
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City |
Tianjin |
State/province |
Tianjin |
ZIP/Postal code |
300060 |
Country |
China |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (12)
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Relations |
BioProject |
PRJNA752771 |
SRA |
SRP331454 |
Supplementary file |
Size |
Download |
File type/resource |
GSE181632_SK-BR-3_SK-EPI.txt.gz |
1002.5 Kb |
(ftp)(http) |
TXT |
GSE181632_SK-EPI-sINC_SK-EPI-siBCRP.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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