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Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment

Overview of attention for article published in BMC Cancer, June 2018
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Title
Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment
Published in
BMC Cancer, June 2018
DOI 10.1186/s12885-018-4521-4
Pubmed ID
Authors

Chrysi Xintaropoulou, Carol Ward, Alan Wise, Suzanna Queckborner, Arran Turnbull, Caroline O. Michie, Alistair R. W. Williams, Tzyvia Rye, Charlie Gourley, Simon P. Langdon

Abstract

Novel therapeutic approaches are required to treat ovarian cancer and dependency on glycolysis may provide new targets for treatment. This study sought to investigate the variation of expression of molecular components (GLUT1, HKII, PKM2, LDHA) of the glycolytic pathway in ovarian cancers and the effectiveness of targeting this pathway in ovarian cancer cell lines with inhibitors. Expression of GLUT1, HKII, PKM2, LDHA were analysed by quantitative immunofluorescence in a tissue microarray (TMA) analysis of 380 ovarian cancers and associations with clinicopathological features were sought. The effect of glycolysis pathway inhibitors on the growth of a panel of ovarian cancer cell lines was assessed by use of the SRB proliferation assay. Combination studies were undertaken combining these inhibitors with cytotoxic agents. Mean expression levels of GLUT1 and HKII were higher in high grade serous ovarian cancer (HGSOC), the most frequently occurring subtype, than in non-HGSOC. GLUT1 expression was also significantly higher in advanced stage (III/IV) ovarian cancer than early stage (I/II) disease. Growth dependency of ovarian cancer cells on glucose was demonstrated in a panel of ovarian cancer cell lines. Inhibitors of the glycolytic pathway (STF31, IOM-1190, 3PO and oxamic acid) attenuated cell proliferation in platinum-sensitive and platinum-resistant HGSOC cell line models in a concentration dependent manner. In combination with either cisplatin or paclitaxel, 3PO (a novel PFKFB3 inhibitor) enhanced the cytotoxic effect in both platinum sensitive and platinum resistant ovarian cancer cells. Furthermore, synergy was identified between STF31 (a novel GLUT1 inhibitor) or oxamic acid (an LDH inhibitor) when combined with metformin, an inhibitor of oxidative phosphorylation, resulting in marked inhibition of ovarian cancer cell growth. The findings of this study provide further support for targeting the glycolytic pathway in ovarian cancer and several useful combinations were identified.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 46 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 17%
Student > Ph. D. Student 6 13%
Student > Bachelor 6 13%
Student > Postgraduate 4 9%
Student > Doctoral Student 3 7%
Other 8 17%
Unknown 11 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 33%
Medicine and Dentistry 6 13%
Pharmacology, Toxicology and Pharmaceutical Science 3 7%
Chemistry 2 4%
Environmental Science 1 2%
Other 5 11%
Unknown 14 30%

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 14 February 2019.
All research outputs
#11,356,810
of 14,322,164 outputs
Outputs from BMC Cancer
#3,538
of 5,442 outputs
Outputs of similar age
#206,681
of 276,381 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
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So far Altmetric has tracked 5,442 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
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