| Title |
Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer
|
|---|---|
| Published in |
Clinical & Experimental Metastasis, March 2017
|
| DOI | 10.1007/s10585-017-9840-3 |
| Pubmed ID | |
| Authors |
Ken Sasaki, Hiroshi Kurahara, Eric D. Young, Shoji Natsugoe, Asami Ijichi, Tomoo Iwakuma, Danny R Welch |
| Abstract |
The overwhelming majority of pancreatic ductal adenocarcinoma (PDAC) is not diagnosed until the cancer has metastasized, leading to an abysmal average life expectancy (3-6 months post-diagnosis). Earlier detection and more effective treatments have been hampered by inadequate understanding of the underlying molecular mechanisms controlling metastasis. We hypothesized that metastasis suppressors are involved in controlling metastasis in pancreatic cancer. Using an unbiased genome-wide shRNA screen, an shRNA library was transduced into the non-metastatic PDAC line S2-028 followed by intrasplenic injection. Resulting liver metastases were individually isolated from these mice. One liver metastatic nodule contained shRNA for ITIH5 (Inter-alpha-trypsin inhibitor heavy chain 5), suggesting that ITIH5 may act as a metastasis suppressor. Consistent with this notion, metastatic PDAC cell lines had significantly lower protein expression of ITIH5 compared to immortalized pancreatic ductal epithelial cells and non-/poorly-metastatic PDAC cell lines. By manipulating expression of ITIH5 in different PDAC cell lines (over-expression in metastatic, knockdown in non-metastatic) functional and selective regulation of metastasis was observed for ITIH5. Orthotopic tumor growth of PDAC cells was not blocked following orthotopic injection. In vitro ITIH5 over-expression inhibited motility and invasion. Immunohistochemical analysis of a human PDAC tissue microarray revealed that ITIH5 expression inversely correlated with both survival and invasion/metastasis. ITIH5 is, therefore, functionally validated as a PDAC metastasis suppressor and shows promise as a prognostic biomarker. |
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 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 40 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 15% |
| Student > Ph. D. Student | 5 | 13% |
| Other | 4 | 10% |
| Student > Postgraduate | 4 | 10% |
| Student > Doctoral Student | 3 | 8% |
| Other | 6 | 15% |
| Unknown | 12 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 16 | 40% |
| Medicine and Dentistry | 6 | 15% |
| Agricultural and Biological Sciences | 2 | 5% |
| Nursing and Health Professions | 1 | 3% |
| Neuroscience | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 13 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 02 July 2019.
All research outputs
#7,210,180
of 23,854,458 outputs
Outputs from Clinical & Experimental Metastasis
#183
of 778 outputs
Outputs of similar age
#110,987
of 311,164 outputs
Outputs of similar age from Clinical & Experimental Metastasis
#3
of 7 outputs
Altmetric has tracked 23,854,458 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 778 research outputs from this source. They receive a mean Attention Score of 4.0. This one has done well, scoring higher than 76% 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 311,164 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 63% of its contemporaries.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.