| Title |
STAT1 modification improves therapeutic effects of interferons on lung cancer cells
|
|---|---|
| Published in |
Journal of Translational Medicine, September 2015
|
| DOI | 10.1186/s12967-015-0656-0 |
| Pubmed ID | |
| Authors |
Junjie Chen, Jialu Zhao, Lefu Chen, Nian Dong, Zhaojian Ying, Zhenzhen Cai, Dongxiang Ji, Yong Zhang, Li Dong, Yuping Li, Lei Jiang, Michael J. Holtzman, Chengshui Chen |
| Abstract |
Interferons (IFNs) have potent anti-proliferative, pro-apoptotic, and immunomodulatory activities against cancer. However, the clinical utility of IFNs is limited by toxicity and pharmacokinetics making it difficult to achieve sustained therapeutic levels especially in solid tumors. Signal Transducer and Activator of Transcription 1 (STAT1) or a modified STAT1 (designated STAT1-CC) that is hyper-responsive to IFN were overexpressed in lung cancer SPC-A-1 and H1299 cells using lentiviral vectors. Transduction efficiency was monitored using enhanced green fluorescent protein (EGFP) expression. After transduction, cells were treated with interferon-gamma (IFN-γ) or interferon-beta (IFN-β) and monitored for cell proliferation, migration, and invasiveness using Cell Counting Kit-8 and transwell chamber assays and for apoptosis using Annexin V detection by flow cytometry. In addition, levels of STAT1, STAT1 Tyr-701 phosphorylation (pSTAT1), fibronectin, and β-catenin were determined using western blotting. In the case of IFN-γ stimulation, levels of S100A4, proliferating cell nuclear antigen (PCNA), and c-fos expression were also determined. We found that expression of STAT1 or STAT1-CC enhanced the effect of IFN-γ and, IFN-β on inhibition of human lung cancer cell proliferation, migration and invasiveness. Moreover, STAT1 and STAT1-CC expression caused increases in pSTAT1 and decreases in fibronectin and β-catenin levels. STAT1-CC showed increased effects compared to STAT1 on IFN-γ induced pSTAT1 and down-regulation of S100A4, PCNA, and c-fos levels. The results show that STAT1-CC exhibited more strength in improving the antitumor response of IFNs in lung cancer cells. Results from this study suggest that combined treatment of IFNs and STAT1-CC might be a feasible approach for the clinical management of lung cancer in the future. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 50% |
| Scientists | 1 | 25% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
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 > Bachelor | 5 | 21% |
| Student > Master | 3 | 13% |
| Student > Doctoral Student | 2 | 8% |
| Student > Postgraduate | 2 | 8% |
| Student > Ph. D. Student | 2 | 8% |
| Other | 4 | 17% |
| Unknown | 6 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 29% |
| Biochemistry, Genetics and Molecular Biology | 5 | 21% |
| Agricultural and Biological Sciences | 2 | 8% |
| Psychology | 1 | 4% |
| Neuroscience | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 8 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 16 September 2015.
All research outputs
#13,212,868
of 22,826,360 outputs
Outputs from Journal of Translational Medicine
#1,521
of 3,994 outputs
Outputs of similar age
#122,487
of 267,498 outputs
Outputs of similar age from Journal of Translational Medicine
#34
of 89 outputs
Altmetric has tracked 22,826,360 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,994 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. This one has gotten more attention than average, scoring higher than 60% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,498 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
We're also able to compare this research output to 89 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.