The prognostic and therapeutic implications of distinct patterns of argininosuccinate synthase 1 (ASS1) and arginase-2 (ARG2) expression by cancer cells and tumor stroma in non-small-cell lung cancer
ConclusionsARG2 and ASS1 enzymes are extensively expressed in NSCLC stroma and cancer cells, respectively. Auxotrophic tumors have a poor prognosis, potentially by utilizing Arg, thus reducing Arg-dependent TIL anti-tumor activity. ASS1 expression in cancer cells would allow Arg fueling ofiNOS+TILs and enhance anti-tumor immunity. However, upregulation of ARG2 in CAFs may divert Arg from TILs, allowing immune escape. Identification of these three distinct phenotypes may be useful in the individualization of Arg-targeting therapies and immunotherapy. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - August 3, 2021 Category: Cancer & Oncology Source Type: research
Inflammatory metabolic profile of South African patients with prostate cancer
ConclusionsFor the first time, a portrait of the metabolic changes in African men with PCa has been delineated indicating a strong association between inflammation and metabolic profiles. Our findings indicate how the metabolic profile could be used to identify those patients with high level of inflammation, characterized by aggressive PCa and short life expectancy. Integrating a metabolomic analysis as a tool for patient stratification could be important for opening the door to the development of new therapies. Further investigations are needed to understand the prevalence of an inflammatory metabotype in patients with ag...
Source: Cancer and Metabolism - August 3, 2021 Category: Cancer & Oncology Source Type: research
Impaired anaplerosis is a major contributor to glycolysis inhibitor toxicity in glioma
ConclusionTogether, these data suggest that at least forENO1-deleted gliomas, tumors in vivo —unlike cells in culture—show limited dependence on glutaminolysis and instead primarily depend on glycolysis for anaplerosis. Our findings reinforce the previously reported metabolic idiosyncrasies of in vitro culture and suggest that cell culture media nutrient composition more faithful to the in vivo environment will more accurately predict in vivo efficacy of metabolism targeting drugs. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - June 25, 2021 Category: Cancer & Oncology Source Type: research
Mass spectrometry imaging of L-[ring-13C6]-labeled phenylalanine and tyrosine kinetics in non-small cell lung carcinoma
ConclusionsWe demonstrated the spatiotemporal intra-tumoral distribution of the essential aromatic amino acid13C6-Phe and its de-novo synthesized metabolite13C6-Tyr by MALDI-FTICR-MSI. Our results explore for the first time local phenylalanine metabolism in the context of cancer tissue morphology. This opens a new way to understand amino acid metabolism within the tumor and its microenvironment. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - June 11, 2021 Category: Cancer & Oncology Source Type: research
The effect of metabolic syndrome on head and neck cancer incidence risk: a population-based prospective cohort study
ConclusionsMS are not correlated with elevated HNC risk. High waist circumference and blood glucose are independent risk factor of HNC incidence. Controlling HDL-C in an appropriate range can get the lowest risk of male HNC. No joint effect of MS and CRP exists in HNC tumorigenesis. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - June 3, 2021 Category: Cancer & Oncology Source Type: research
Inhibition of glycolysis and mitochondrial respiration promotes radiosensitisation of neuroblastoma and glioma cells
ConclusionOur findings demonstrate that the radiosensitising effect of 2-DG was significantly enhanced by its combination with metformin. This clearly demonstrates that dual metabolic targeting has potential to improve clinical outcomes in children with high-risk neuroblastoma by overcoming radioresistance. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 19, 2021 Category: Cancer & Oncology Source Type: research
Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor- κB/snail/hexokinase3 signaling axis in colorectal cancer
ConclusionLPS activates inflammasomes in cancer cells through NF- κB and promotes metastasis through glycolysis enhanced by the NF-κB/Snail/HK3 signaling pathway in CRC. Metformin could prevent this effect of LPS. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 12, 2021 Category: Cancer & Oncology Source Type: research
DHODH and cancer: promising prospects to be explored
AbstractHuman dihydroorotate dehydrogenase (DHODH) is a flavin-dependent mitochondrial enzyme catalyzing the fourth step in the de novo pyrimidine synthesis pathway. It is originally a target for the treatment of the non-neoplastic diseases involving in rheumatoid arthritis and multiple sclerosis, and is re-emerging as a validated therapeutic target for cancer therapy. In this review, we mainly unravel the biological function of DHODH in tumor progression, including its crucial role in de novo pyrimidine synthesis and mitochondrial respiratory chain in cancer cells. Moreover, various DHODH inhibitors developing in the past...
Source: Cancer and Metabolism - May 10, 2021 Category: Cancer & Oncology Source Type: research
High-resolution spatiotemporal pHe and pO2 imaging in head and neck and oesophageal carcinoma cells
ConclusionsWe developed a method to spatiotemporally measure OCR and ECAR of cells, which has many potential in vitro applications and lays the foundation for the development of novel diagnostic tools for the detection of cancerous tissue in HNSCC and ESCC patients in vivo. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 4, 2021 Category: Cancer & Oncology Source Type: research
High-resolution spatiotemporal pH e and pO 2 imaging in head and neck and oesophageal carcinoma cells
ConclusionsWe developed a method to spatiotemporally measure OCR and ECAR of cells, which has many potential in vitro applications and lays the foundation for the development of novel diagnostic tools for the detection of cancerous tissue in HNSCC and ESCC patients in vivo. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 4, 2021 Category: Cancer & Oncology Source Type: research
Pyruvate carboxylase and cancer progression
AbstractPyruvate carboxylase (PC) is a mitochondrial enzyme that catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate (OAA), serving to replenish the tricarboxylic acid (TCA) cycle. In nonmalignant tissue, PC plays an essential role in controlling whole-body energetics through regulation of gluconeogenesis in the liver, synthesis of fatty acids in adipocytes, and insulin secretion in pancreatic β cells. In breast cancer, PC activity is linked to pulmonary metastasis, potentially by providing the ability to utilize glucose, fatty acids, and glutamine metabolism as needed under varying conditions as cells m...
Source: Cancer and Metabolism - April 30, 2021 Category: Cancer & Oncology Source Type: research
TNF- α differentially modulates subunit levels of respiratory electron transport complexes of ER/PR +ve/−ve breast cancer cells to regulate mitochondrial complex activity and tumorigenic potential
ConclusionThe evidence presented in our study convincingly demonstrates that TNF- α regulates the survival and proliferation of aggressive tumor cells by modulating the levels of critical assembly factors and subunits involved in mitochondrial respiratory chain supercomplexes organization and function. This favors the rewiring of mitochondrial metabolism towards anaplerosis to s upport the survival and proliferation of breast cancer cells. Collectively, the results strongly suggest that TNF-α differentially regulates metabolic adaptation in ER/PR +ve (MCF-7) and ER/PR −ve (MDA-MB-231) cells by modulating the mitochondr...
Source: Cancer and Metabolism - April 29, 2021 Category: Cancer & Oncology Source Type: research
Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness
ConclusionsIn glioblastoma, particularly in the mesenchymal subtype, the downregulation of both genes and proteins (GLUD1 and GPT2) increases the source of glutamate for GSH synthesis and enhances tumor cell fitness due to increased antioxidative capacity. In contrast, in lower-grade astrocytoma, mainly in those harboring theIDH1 mutation, the gene expression profile indicates that tumor cells might be sensitized to oxidative stress due to reduced GSH synthesis. The measurement ofGLUD1 andGPT2 metabolic substrates, ammonia, and alanine, by noninvasive MR spectroscopy, may potentially allow the identification ofIDH1mut AGII...
Source: Cancer and Metabolism - April 28, 2021 Category: Cancer & Oncology Source Type: research
Mitochondrial metabolism as a target for acute myeloid leukemia treatment
AbstractAcute myeloid leukemias (AML) are a group of aggressive hematologic malignancies resulting from acquired genetic mutations in hematopoietic stem cells that affect patients of all ages. Despite decades of research, standard chemotherapy still remains ineffective for some AML subtypes and is often inappropriate for older patients or those with comorbidities. Recently, a number of studies have identified unique mitochondrial alterations that lead to metabolic vulnerabilities in AML cells that may present viable treatment targets. These include mtDNA, dependency on oxidative phosphorylation, mitochondrial metabolism, a...
Source: Cancer and Metabolism - April 21, 2021 Category: Cancer & Oncology Source Type: research
Tumor suppressor SMAR1 regulates PKM alternative splicing by HDAC6-mediated deacetylation of PTBP1
ConclusionsSMAR1 regulatesPKM alternative splicing by causing HDAC6-dependent deacetylation of PTBP1, resulting in reduced enrichment of PTBP1 onPKM pre-mRNA. Additionally, SMAR1 suppresses glucose utilization and lactate production via repression of PKM2 expression. This suggests that tumor suppressor SMAR1 inhibits tumor cell metabolism and tumorigenic properties of cancer cells via regulation ofPKM alternative splicing. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - April 16, 2021 Category: Cancer & Oncology Source Type: research
