Cancer & Metabolism

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BACKGROUND: To support proliferation and survival within a challenging microenvironment, cancer cells must reprogramme their metabolism. As such, targeting cancer cell metabolism is a promising therapeutic avenue. However, identifying tractable nodes of metabolic vulnerability in cancer cells is challenging due to their metabolic plasticity. Identification of effective treatment combinations to counter this is an active area of research. Aspirin has a well-established role in cancer prevention, particularly in colorectal cancer (CRC), although the mechanisms are not fully understood...

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, but if discovered at an early stage, the survival rate is high. The aim of this study was to identify novel markers predictive of future CRC risk using untargeted metabolomics. METHODS: This study included prospectively collected plasma samples from 902 CRC cases and 902 matched cancer-free control participants from the population-based Northern Sweden Health and Disease Study (NSHDS), which were obtained up to 26 years prior to CRC diagnosis...

BACKGROUND: Endometrial cancer (EMC) is the most common female genital tract malignancy with an increasing prevalence in many countries including Japan, a fact that renders early detection and treatment necessary to protect health and fertility. Although early detection and treatment are necessary to further improve the prognosis of women with endometrial cancer, biomarkers that accurately reflect the pathophysiology of EMC patients are still unclear. Therefore, it is clinically critical to identify biomarkers to assess diagnosis and treatment efficacy to facilitate appropriate treatment and development of new therapies for EMC...

Hypercholesterolemia is often correlated with obesity which is considered a risk factor for various cancers. With the growing population of hypercholesterolemic individuals, there is a need to understand the role of increased circulatory cholesterol or dietary cholesterol intake towards cancer etiology and pathology. Recently, abnormality in the blood cholesterol level of colon cancer patients has been reported. In the present study, we demonstrate that alteration in cholesterol levels (through a high-cholesterol or high-fat diet) increases the incidence of chemical carcinogen-induced colon polyp occurrence and tumor progression in mice...

BACKGROUND: Tissue environment is critical in determining tumour metabolic vulnerability. However, in vivo drug testing is slow and waiting for tumour growth delay may not be the most appropriate endpoint for metabolic treatments. An in vivo method for measuring energy stress would rapidly determine tumour targeting in a physiologically relevant environment. The sodium-iodide symporter (NIS) is an imaging reporter gene whose protein product co-transports sodium and iodide, and positron emission tomography (PET) radiolabelled anions into the cell...

BACKGROUND: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there...

The use of bacteria in cancer immunotherapy has the potential to bypass many shortcomings of conventional treatments. The ability of anaerobic bacteria to preferentially accumulate and replicate in hypoxic regions of solid tumors, as a consequence of bacterial metabolic needs, is particularly advantageous and key to boosting their immunostimulatory therapeutic actions in situ. While several of these bacterial traits are well-studied, little is known about their competition for nutrients and its effect on cancer cells which could serve as another potent and innate antineoplastic action...

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is the major histological subtype of kidney tumor which covers approximately 80% of the cases. Although various therapies have been developed, the clinical outcome remains unsatisfactory. Metabolic dysregulation is a key feature of KIRC, which impacts progression and prognosis of the disease. Therefore, understanding of the metabolic changes in KIRC is of great significance in improving the treatment outcomes. METHODS: The glycolysis/gluconeogenesis genes were analyzed in the KIRC transcriptome from the Cancer Genome Atlas (TCGA) by the different expression genes (DEGs) test and survival analysis...

Melanoma is considered as the most common metastatic skin cancer with increasing incidence and high mortality globally. The vital roles of long non-coding RNAs (lncRNAs) in the tumorigenesis of melanoma are elucidated by emerging evidence. The lncRNA cervical carcinoma high-expressed 1 (CCHE1) was overexpressed and acted as an oncogene in a variety of cancers, while the function of CCHE1 in melanoma remains unclear. Here, we found that CCHE1 was highly expressed in melanoma and correlated with the poorer survival of melanoma patients...

BACKGROUND: Excessive hepatic glycogen accumulation benefits tumorigenesis and cancer cell survival. We previously reported that BMP4 has the strongest ability to promote glycogenesis among the 14 BMPs in hepatocytes and augmented hepatocellular carcinoma (HCC) cell survival under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway. However, the mechanism underlying BMP4's effect on glycogenesis in HCC remains elusive. METHODS: The expression of BMP4 and SLC2A1 were acquired by analyzing the TCGA-LIHC dataset, as well as by immunohistochemical analysis of the 40 pairs of human HCC samples and para-tumor tissues...

PURPOSE: Examine the association between obesity and clinical outcomes in early breast cancer and assess if patient, tumor, and treatment characteristics modify such associations in Malmö Diet and Cancer Study patients (MDCS). METHODS: The MDCS enrolled 17,035 Swedish women from 1991 to 1996. At enrollment, participants' body mass index (BMI), waist circumference and body fat percentage measures were collected. We identified all female MDCS participants with invasive breast cancer from 1991 to 2014...

BACKGROUND: The impact of non-small cell lung cancer (NSCLC) metabolism on the immune microenvironment is not well understood within platinum resistance. We have identified crucial metabolic differences between cisplatin-resistant (CR) and cisplatin-sensitive (CS) NSCLC cells with elevated indoleamine 2,3-dioxygenase-1 (IDO1) activity in CR, recognized by increased kynurenine (KYN) production. METHODS: Co-culture, syngeneic, and humanize mice models were utilized...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC's excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear. METHODS: We performed a phase 1b observational study (ClinicalTrials...

BACKGROUND: Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP activation limits non-alcoholic fatty liver disease (NAFLD) in hepatic GSD Ia...

Gene expression signatures associated with breast cancer metastases suggest that metabolic re-wiring is important for metastatic growth in lungs, bones, and other organs. However, since pathway fluxes depend on additional factors such as ATP demand, allosteric effects, and post-translational modification, flux analysis is necessary to conclusively establish phenotypes. In this study, the metabolic phenotypes of breast cancer cell lines with low (T47D) or high (MDA-MB-231) metastatic potential, as well as lung (LM)- and bone (BoM)-homing lines derived from MDA-MB-231 cells, were assessed by 13 C metabolite labeling from [1,2-13 C] glucose or [5-13 C] glutamine and the rates of nutrient and oxygen consumption and lactate production...

BACKGROUND: Recently, we reported that tamoxifen-resistant (TAM-R) breast cancer cells are cross-resistant to irradiation. Here, we investigated the mechanisms associated with tamoxifen-induced radioresistance, aiming to prevent or reverse resistance and improve breast cancer treatment. METHODS: Wild-type ERα-positive MCF7 and ERα-negative MDA-MB-231 breast cancer cells and their TAM-R counterparts were analyzed for cellular metabolism using the Seahorse metabolic analyzer...

Acute lymphoblastic leukemia (ALL) and its treatment continue to pose substantial risks. To understand ALL more deeply, the metabolome in fasting plasma of 27 ALL patients before and after high-dose methotrexate therapies (consolidation therapy) including methotrexate and 6-mercaptopurine (6-MP) was investigated. Plasma metabolites were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS). Orthogonal projections to latent structures discriminant analysis and significance analysis of microarrays were used to evaluate the metabolic changes...

BACKGROUND: Arginase-1 (ARG1), a urea cycle-related enzyme, catalyzes the hydrolysis of arginine to urea and ornithine, which regulates the proliferation, differentiation, and function of various cells. However, it is unclear whether ARG1 controls the progression and malignant alterations of colon cancer. METHODS: We established metastatic colonization mouse model and ARG1 overexpressing murine colon cancer CT26 cells to investigate whether activation of ARG1 was related to malignancy of colon cancer cells in vivo...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichment of glycolytic genes in the more aggressive and therapy-resistant QM subtype. However, whether the glycolytic transcripts are translated into functional glycolysis that could further be explored for metabolic targeting in QM subtype is still not known...