Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
154-319 |
DRI_Background |
denotes |
The triple-negative phenotype is the most prevalent form of human breast cancer worldwide and is characterized by poor survival, high aggressiveness, and recurrence. |
T2 |
320-483 |
DRI_Background |
denotes |
Microvesicles (MV) are shredded plasma membrane components and critically mediate cell-cell communication, but can also induce cancer proliferation and metastasis. |
T3 |
484-725 |
DRI_Background |
denotes |
Previous studies have revealed that protease-activated receptor 2 (PAR2) contributes significantly to human triple-negative breast cancer (TNBC) progression by releasing nano-size MV and promoting cell proliferation, migration, and invasion. |
T4 |
726-829 |
DRI_Background |
denotes |
MV isolated from highly aggressive human TNBC cells impart metastatic potential to nonmetastatic cells. |
T5 |
830-1000 |
DRI_Background |
denotes |
Over-expression of microRNA221 (miR221) has also been reported to enhance the metastatic potential of human TNBC, but miR221's relationship to PAR2-induced MV is unclear. |
T6 |
1001-1342 |
DRI_Outcome |
denotes |
Here, using isolated MV, immunoblotting, quantitative RT-PCR, FACS analysis, and enzymatic assays, we show that miR221 is translocated via human TNBC-derived MV, which upon fusion with recipient cells, enhance their proliferation, survival, and metastasis both in vitro and in vivo by inducing the epithelial-to-mesenchymal transition (EMT). |
T7 |
1343-1572 |
DRI_Background |
denotes |
Administration of anti-miR221 significantly impaired MV-induced expression of the mesenchymal markers Snail, Slug, N-cadherin, and vimentin in the recipient cells, whereas restoring expression of the epithelial marker E-cadherin. |
T8 |
1573-1597 |
DRI_Outcome |
denotes |
We also demonstrate that |
T9 |
1619-1763 |
DRI_Outcome |
denotes |
targets phosphatase and tensin homolog (PTEN) in the recipient cells, followed by AKT Ser/Thr kinase (AKT)/NF-κB activation, which promotes EMT. |
T10 |
1764-1909 |
DRI_Background |
denotes |
Moreover, elevated miR221 levels in MV derived from human TNBC patients' blood could induce cell proliferation and metastasis in recipient cells. |
T11 |
1910-2042 |
DRI_Approach |
denotes |
In summary, miR221 transfer from TNBC cells via PAR2-derived MV induces EMT and enhances the malignant potential of recipient cells. |