| Title |
Transketolase is upregulated in metastatic peritoneal implants and promotes ovarian cancer cell proliferation
|
|---|---|
| Published in |
Clinical & Experimental Metastasis, April 2015
|
| DOI | 10.1007/s10585-015-9718-1 |
| Pubmed ID | |
| Authors |
Carmela Ricciardelli, Noor A. Lokman, Sowmya Cheruvu, Izza A. Tan, Miranda P. Ween, Carmen E. Pyragius, Andrew Ruszkiewicz, Peter Hoffmann, Martin K. Oehler |
| Abstract |
Ovarian cancer, the most lethal gynaecological cancer, is characterised by the shedding of epithelial cells from the ovarian surface, followed by metastasis and implantation onto the peritoneal surfaces of abdominal organs. Our proteomic studies investigating the interactions between peritoneal (LP-9) and ovarian cancer (OVCAR-5) cells found transketolase (TKT) to be regulated in the co-culture system. This study characterized TKT expression in advanced stage (III/IV) serous ovarian cancers (n = 125 primary and n = 54 peritoneal metastases), normal ovaries (n = 6) and benign serous cystadenomas (n = 10) by immunohistochemistry. In addition, we also evaluated the function of TKT in ovarian cancer cells in vitro. Nuclear TKT was present in all primary serous ovarian cancer tissues examined (median 82.0 %, range 16.5-100 %) and was significantly increased in peritoneal metastases compared with matching primary cancers (P = 0.01, Wilcoxon Rank test). Kaplan-Meier survival and Cox regression analyses showed that high nuclear TKT positivity in peritoneal metastases (>94 %) was significantly associated with reduced overall survival (P = 0.006) and a 2.8 fold increased risk of ovarian cancer death (95 % CI 1.29-5.90, P = 0.009). Knockdown of TKT by siRNAs significantly reduced SKOV-3 cell proliferation but had no effect on their motility or invasion. Oxythiamine, an inhibitor of TKT activity, significantly inhibited the proliferation of four ovarian cancer cell lines (OV-90, SKOV-3, OVCAR-3 and OVCAR-5) and primary serous ovarian cancer cells isolated from patient ascites. In conclusion, these findings indicate that TKT plays an important role in the proliferation of metastatic ovarian cancer cells and could be used as novel therapeutic target for advanced disease. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 42 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 24% |
| Student > Ph. D. Student | 7 | 17% |
| Student > Master | 6 | 14% |
| Student > Bachelor | 4 | 10% |
| Student > Doctoral Student | 2 | 5% |
| Other | 6 | 14% |
| Unknown | 7 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 12 | 29% |
| Medicine and Dentistry | 8 | 19% |
| Agricultural and Biological Sciences | 5 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Nursing and Health Professions | 2 | 5% |
| Other | 4 | 10% |
| Unknown | 9 | 21% |
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 26 August 2015.
All research outputs
#19,382,126
of 23,854,458 outputs
Outputs from Clinical & Experimental Metastasis
#603
of 778 outputs
Outputs of similar age
#197,818
of 268,192 outputs
Outputs of similar age from Clinical & Experimental Metastasis
#4
of 10 outputs
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