Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis and Tumor Progression in Mouse Models of Lung Cancer and Impacts Tumor-Initiating Cells
Cell Metabolism, ISSN: 1550-4131, Vol: 19, Issue: 5, Page: 795-809
2014
- 394Citations
- 209Usage
- 410Captures
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations394
- Citation Indexes394
- 394
- CrossRef359
- Usage209
- Downloads186
- Abstract Views23
- Captures410
- Readers410
- 408
Article Description
The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the interconversion of pyruvate and lactate, is upregulated in human cancers, and is associated with aggressive tumor outcomes. Here we use an inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo. This was accompanied by reactivation of mitochondrial function in vitro, but not in vivo or ex vivo. Finally, using a specific small molecule LDH-A inhibitor, we demonstrated that LDH-A is essential for cancer-initiating cell survival and proliferation. Thus, LDH-A can be a viable therapeutic target for NSCLC, including cancer stem cell-dependent drug-resistant tumors.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1550413114001077; http://dx.doi.org/10.1016/j.cmet.2014.03.003; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84900296103&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/24726384; https://linkinghub.elsevier.com/retrieve/pii/S1550413114001077; https://uknowledge.uky.edu/toxicology_facpub/48; https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1047&context=toxicology_facpub; http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00107-7?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413114001077%3Fshowall%3Dtrue; http://www.cell.com/article/S1550413114001077/pdf; http://www.cell.com/article/S1550413114001077/abstract; http://www.cell.com/article/S1550413114001077/fulltext; http://linkinghub.elsevier.com/retrieve/pii/S1550413114001077
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