| Title |
Notch-1 signaling activates NF-κB in human breast carcinoma MDA-MB-231 cells via PP2A-dependent AKT pathway
|
|---|---|
| Published in |
Medical Oncology, March 2016
|
| DOI | 10.1007/s12032-016-0747-7 |
| Pubmed ID | |
| Authors |
Li Li, Jing Zhang, Niya Xiong, Shun Li, Yu Chen, Hong Yang, Chunhui Wu, Hongjuan Zeng, Yiyao Liu |
| Abstract |
Breast cancer has a high incidence in the world and is becoming a leading cause of death in female patients due to its high metastatic ability. High expression of Notch-1 and its ligand Jagged-1 correlates with poor prognosis in breast cancer. Our previous work has shown that Notch-1 signaling pathway upregulates NF-κB transcriptional activity and induces the adhesion, migration and invasion of human breast cancer cell line MDA-MB-231. However, the role of Notch-1 in NF-κB activation is still poorly understood. Here, we aim to understand the exact mechanism that Notch-1 regulates NF-κB activity. In MDA-MB-231 cells where Notch-1 is constitutively activated, the phosphorylation of p85 and AKT (Tyr308/Ser473) is upregulated, indicating PI3K/AKT pathway is activated. Notch-1 activation caused the increase of PP2A phosphorylation at Tyr307, indicating Notch-1 inhibits PP2A activity. NF-κB transcriptional activity was evaluated by dual-luciferase reporter assay, and the results showed that, while silencing of Notch-1, PP2A activity was upregulated and NF-κB activity was downregulated, whereas PP2A inhibitor okadaic acid (OA) restored NF-κB activity. Immunofluorescence and Western blots showed that OA treatment antagonized the decrease of p65 nuclear translocation caused by Notch-1 silencing. Moreover, OA treatment also upregulated MMP-2, MMP-9 and VEGF mRNA expression levels, indicating OA rescues Notch-1 silencing that caused low cell invasion. Taken together, our results suggest that Notch-1-activating PI3K/AKT/NF-κB pathway is PP2A dependent; PP2A may be a potential therapeutic target in breast cancer. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 25% |
| Student > Bachelor | 4 | 17% |
| Student > Master | 4 | 17% |
| Researcher | 2 | 8% |
| Student > Doctoral Student | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 7 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 38% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 8% |
| Agricultural and Biological Sciences | 2 | 8% |
| Computer Science | 1 | 4% |
| Medicine and Dentistry | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 8 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 March 2016.
All research outputs
#20,313,158
of 22,854,458 outputs
Outputs from Medical Oncology
#960
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Outputs of similar age
#252,281
of 298,823 outputs
Outputs of similar age from Medical Oncology
#14
of 19 outputs
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