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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Secretory RAB GTPase 3C modulates IL6-STAT3 pathway to promote colon cancer metastasis and is associated with poor prognosis
|
|---|---|
| Published in |
Molecular Cancer, August 2017
|
| DOI | 10.1186/s12943-017-0687-7 |
| Pubmed ID | |
| Authors |
Yu-Chan Chang, Chia-Yi Su, Ming-Huang Chen, Wei-Shone Chen, Chi-Long Chen, Michael Hsiao |
| Abstract |
RAB GTPases are important in the regulation of membrane trafficking and cell movement. Recently, exocytic RABs have received increasing attention in cancer research. However, the functional roles of exocytic RABs in colorectal carcinogenesis remain to be elucidated. Immunohistochemistry analysis of a microarray containing 215 colorectal adenocarcinoma tissues was used to identify the association between exocytic RABs and patient prognosis. Complementary functional RAB3C overexpression and knockdown experiments were performed. The molecular mechanism of RAB3C in inducing colon cancer cell metastasis was determined. High RAB3C expression in patients was found to be significantly associated with advanced pathological stage, distant metastasis and poor prognosis. Multivariate analyses showed that high RAB3C expression was an independent prognostic marker in overall (P = 0.001) and disease-free survival (P < 0.001). Furthermore, our experimental results showed an increase in the migration and invasion ability of RAB3C-overexpressing colon cancer cells and increased metastatic nodules in a mouse metastasis model. The effect of RAB3C-overexpressing cell-conditioned medium was found to significantly promote the migration ability of parental colon cancer cells, thus suggesting that the promotion of migration is exocytosis dependent. Upregulation of other exocytic RABs was also seen in RAB3C-overexpressing cells. Through microarray and proteomics analyses, increased production of multiple cytokines was observed in RAB3C-overexpressing cell lines, and the IL-6 pathway was the top pathway whose members exhibited gene expression changes after RAB3C overexpression, according to Ingenuity Pathway Analysis. Blocking IL-6 with IL-6 antibody treatment or IL-6 knockdown significantly inhibited the migration potential of RAB3C-overexpressing colon cancer cells. In addition, IL-6 was found to induce STAT3 phosphorylation in RAB3C-overexpressing colon cancer cells, thus promoting migration. Ruxolitinib, a JAK2 inhibitor, was found to significantly inhibit RAB3C-induced colon cancer cell migration. Our study revealed that RAB3C overexpression promotes tumor metastasis and is associated with poor prognosis in colorectal cancer, through modulating the ability of cancer cells to release IL-6 through exocytosis and activate the JAK2-STAT3 signaling pathway. These results further suggest that inhibition of STAT3 phosphorylation in the RAB3C-IL-6-STAT3 axis by using Ruxolitinib may be a new therapeutic strategy to combat metastatic colon cancers. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 30 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 23% |
| Student > Ph. D. Student | 6 | 20% |
| Student > Master | 3 | 10% |
| Student > Doctoral Student | 2 | 7% |
| Student > Bachelor | 2 | 7% |
| Other | 4 | 13% |
| Unknown | 6 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 33% |
| Agricultural and Biological Sciences | 3 | 10% |
| Medicine and Dentistry | 3 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 7% |
| Neuroscience | 2 | 7% |
| Other | 3 | 10% |
| Unknown | 7 | 23% |
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 05 November 2017.
All research outputs
#17,913,495
of 22,999,744 outputs
Outputs from Molecular Cancer
#1,208
of 1,731 outputs
Outputs of similar age
#227,749
of 317,747 outputs
Outputs of similar age from Molecular Cancer
#20
of 37 outputs
Altmetric has tracked 22,999,744 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,731 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
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 317,747 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.