1. HypOxystation users Satani et al. examined the efficacy of ENOblock, a promising new drug for the treatment of cancer and diabetes which was thought to inhibit the glycolytic enzyme enolase. In their recent paper “ENOblock Does Not Inhibit the Activity of the Glycolytic Enzyme Enolase”, the group at MD Anderson Cancer Center in Houston used data from X-ray structures, Cellular thermal shift assays and mutational analyses to show that while the biological effects of the cell permeable ENOblock were reproduced in glioma cells cultured under hypoxia (0.1%), the efficacy of the drug must involve other mechanisms than the previously reported direct inhibition of enolase activity.
From: Satani et al. (2016) “ENOblock Does Not Inhibit the Activity of the Glycolytic Enzyme Enolase” PLoS ONE 11(12):e0168739. doi:10.1371
2. Tumor cells must adjust their metabolism to survive the nutrient- and oxygen-deprived environment typical of most cancers. Olivares et al., HypOxystation users of CRCM in Marseille, recently published their findings on the extracellular matrix as a nutrient reservoir for pancreatic ductal adenocarcinoma cells in “Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions”. Collagen uptake, survival, and proliferation assays were conducted at 1% O2 in the oxygen-controlled chamber of the HypOxystation. These results are an important contribution to understanding how targeting proline metabolism can restrict tumor cell survival and slow tumor growth.
From: Olivares et al. (2017) “Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions” NATURE COMMUNICATIONS 8:16031 DOI: 10.1038
3. A recent paper by HypOxystation users Burr et al. of the University of Cambridge in UK provides valuable insights into how “Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls the pathways and factors regulating HIF1a Stability in Aerobic Conditions”. In metabolic and biochemical studies of near-haploid human cells cultured under hypoxia, the group examined small molecule metabolite regulation of hypoxia inducible factors (HIF’s). They identified two mitochondrial genes, oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase (LIAS), which affect epigenetic regulation and tumor development.
From: Burr et al. (2016) “Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls the pathways and factors regulating HIF1a Stability in Aerobic Conditions” Cell Metabolism 25, 740–752
4. Metabolic pathways and the impact of hypoxia on proliferation and survival of small cell lung cancer (SCLC) cells was the topic of a recent publication by Thoren et al. in “Myc-induced glutaminolysis bypasses HIF-driven glycolysis in hypoxic small cell lung carcinoma cells”. SCLC and neuroblastoma cell lines were cultivated in the HypOxystation at 1% O2. Complex interactive pathways involving MYC and HIF regulate ATP production via glutaminolysis, which may be a promising target for treatment of some subsets of SCLC.
From: Thoren et al. (2017) “Myc-induced glutaminolysis bypasses HIF-driven glycolysis in hypoxic small cell lung carcinoma cells” Oncotarget, 2017, Vol. 8, (No. 30), pp: 48983-48995
