Cancer metabolism: looking forward

Martínez‐Reyes, Inmaculada; Chandel, Navdeep S.

doi:10.1038/s41568-021-00378-6

Cited by 873 publications

(663 citation statements)

References 176 publications

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“…The viability promoting effect of NAC overcompensated for the cytotoxic effect of HO-5114 at the concentration of up to 5 µM, but at 10 µM, it failed to do so (Figure 4b). The absence of NAC's effect on HO-5114 s cytotoxicity in the HR+BC line (Figure 4a) indicated not only a reduced chronic oxidative stress in it compared to the TNBC line but also suggested differences in metabolic reprogramming between the two BC cell lines [27].…”

Section: Discussionmentioning

confidence: 99%

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

Andreidesz

Szabó

Kovács

et al. 2021

IJMS

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Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug’s anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer; however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential.

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Section: Discussionmentioning

confidence: 99%

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

Andreidesz

Szabó

Kovács

et al. 2021

IJMS

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“…GO analysis suggested that the driver genes were enriched in metabolism-related functions, including serine-type endopeptidase inhibitor activity, peptidase inhibitor activity and phosphoric ester hydrolase activity. Tumor cells undergo metabolic reprogramming during tumorigenesis to satisfy the requirements for enhanced biologic energy and biological synthesis and to alleviate the oxidative stress from increased proliferation and survival of tumor cells [40]. We evaluated the distribution of somatic variations in EC driver genes between low and high ICI subsets.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer

Chen

Huang

Peng

et al. 2021

Preprint

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Background. Esophageal cancer (EC) is the 7th most common neoplasm and the 6th most common cause of cancer-related death worldwide. Immunotherapy is an effective treatment for EC patients. However, there are no dependable markers for predicting prognosis and immunotherapy responses in EC. Our study aims to explore prognostic models and markers in EC as well as predictors for immunotherapy. Methods. The expression profiles of EC were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases. Cox regression analysis was performed to construct a prognostic model. Overall survival and receiver operating characteristic curve analyses were applied to verify the accuracy of the model. The CIBERSORT algorithm was conducted to quantify the infiltration of different immune cells, and EC was grouped into three immune cell infiltration (ICI) clusters. PD-1 and PD-L1 expressions were compared between the ICI clusters. Overall survival analysis between ICI score and tumor mutation burden was conducted. The immunotherapy response of patients in different ICI score clusters was also compared. The copy number variations, somatic mutations, and single nucleotide polymorphisms were analyzed. Enrichment analyses were also performed. Results. A prognostic model was successfully constructed. Three ICI clusters were identified, and the clusters with high immune and stromal scores tended to have more immune-activated phenotypes and higher expressions of PD-1 and PDL1. The ICI score may be used as a predictor independent of tumor mutation burden. Patients with higher ICI score tended to have better immunotherapeutic responses than those with lower scores. Enrichment analyses showed that the differentially expressed genes were mostly enriched in microvillus and the KRAS and IL6/JAK/STAT3 pathways. The top eight genes with the highest mutation frequencies in EC were identified and all related to the prognosis of EC patients. Conclusions. Our study established an effective prognostic model and identified markers for predicting the prognosis and immunotherapy response of EC patients.

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“…The class with strongest transmembrane helix density, containing 2,395,948 particles, was further subjected to 3D classification (k=4, 20 iterations at 7.5º sampling) against its corresponding volume lowpassfiltered to 15 Å. Particles (1,557,854) selected from the dominant class were subjected to 3D auto-refinement against its own map (lowpass-filtered to 15 Å), resulting in a 4.1 Å reconstruction. These particles were Bayesian polished and further classified in 2D (k=200), generating a subset of 964,303 cleaned and polished particles.…”

Section: Cryo-em Sample Preparation and Data Acquisitionmentioning

confidence: 99%

Molecular basis for redox control by the human cystine/glutamate antiporter System xc^-

Parker

Deme

Kolokouris

et al. 2021

Preprint

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Cysteine plays an essential role in cellular redox homeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step in cellular GSH synthesis is the availability of cysteine. However, circulating cysteine exists in the blood as the oxidised di-peptide cystine, requiring specialised transport systems for its import into the cell. System xc- is a dedicated cystine transporter, importing cystine in exchange for intracellular glutamate. To counteract elevated levels of reactive oxygen species in cancerous cells system xc- is frequently upregulated, making it an attractive target for anticancer therapies. However, the molecular basis for ligand recognition and transport remains elusive, hampering efforts to specifically target this system. Here we present the cryo-EM structure of system xc- in both the apo and glutamate bound states. Structural comparisons reveal an allosteric mechanism for ligand discrimination, supported by molecular dynamics and cell-based assays, establishing a mechanism for cystine recognition and transport in human cells.

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Cancer metabolism: looking forward

Cited by 873 publications

References 176 publications

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer

Molecular basis for redox control by the human cystine/glutamate antiporter System xc^-

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Cancer metabolism: looking forward

Cited by 873 publications

References 176 publications

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

­ Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer

Molecular basis for redox control by the human cystine/glutamate antiporter System xc-

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Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer

Molecular basis for redox control by the human cystine/glutamate antiporter System xc^-