scholarly journals A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 18309-18324 ◽  
Author(s):  
Anna Vert ◽  
Jessica Castro ◽  
Marc Ribó ◽  
Antoni Benito ◽  
Maria Vilanova
Keyword(s):  
Cancer Cells ◽  
Metabolic Phenotype ◽  
Pancreatic Ribonuclease ◽  
Human Pancreatic Ribonuclease

scholarly journals Endowing Human Pancreatic Ribonuclease with Toxicity for Cancer Cells

2001 ◽  
Vol 276 (46) ◽  
pp. 43095-43102 ◽  
Author(s):  
Peter A. Leland ◽  
Kristine E. Staniszewski ◽  
Byung-Moon Kim ◽  
Ronald T. Raines
Keyword(s):  
Cancer Cells ◽  
Pancreatic Ribonuclease ◽  
Human Pancreatic Ribonuclease

scholarly journals TAMI-57. MEDULLOBLASTOMA UTILIZE GABA TRANSAMINASE TO SURVIVE IN THE CEREBROSPINAL FLUID MICROENVIRONMENT AND PROMOTE LEPTOMENINGEAL DISSEMINATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii225-ii226
Author(s):  
Vahan Martirosian ◽  
Krutika Deshpande ◽  
Hao Zhou ◽  
Keyue Shen ◽  
Vazgen Stepanosyan ◽  
...  
Keyword(s):  
Energy Source ◽  
Cerebrospinal Fluid ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Leptomeningeal Metastases ◽  
Metabolic Phenotype ◽  
Leptomeningeal Disease ◽  
Neural Cells ◽  
Gaba Transaminase

Abstract Medulloblastoma (MB) is a malignant pediatric brain tumor. Studies have shown heterogeneous cells amongst the tumor bulk which mirror normal neural cells in various neurodevelopmental stages. To discern exploited mechanisms promoting MB leptomeningeal disease, we drew conclusions from developmental neurobiology. In normal differentiation, the metabolic phenotype in proliferating neural progenitor cells evolves from a glycolysis-dependent to an oxidative phosphorylation-reliant energetic profile in quiescent differentiated neurons. Cancer cells mirror this evolution, which also grants them the capability to utilize alternative nutrients in the microenvironment as an energy source. Considering metastatic cells are typically in a dormant state and primarily utilize oxidative phosphorylation, we hypothesized metastatic MB cells emulate a quiescent neuron-like cellular profile to survive in the cerebrospinal fluid and form leptomeningeal metastases. To examine this, we query the expression of GABA catabolic enzyme GABA transaminase (ABAT) in MB. GABA is found in the cerebellar and leptomeningeal microenvironments, and is utilized by metastatic cancer cells in the CNS as an energy source. We correlate an increase in ABAT expression with neurodevelopment and show heterogeneous expression of this protein in primary MB tumors. MB cells with increased expression of ABAT were slower-dividing, expressed a genetic and metabolic phenotype reminiscent of quiescent neuron-like cells, and had increased capability to metabolize GABA. Conversely, lower expression of ABAT was associated with an increased proliferation rate and correlated with a progenitor-like cellular profile. Transplantation of MB cells into the leptomeningeal compartment decreased proliferative capacity and enhanced ABAT expression. Xenograft models showed MB cells with ABAT knockdown had increased growth in the cerebellar microenvironment. Conversely, MB cells with ABAT overexpression transplanted into the cerebrospinal fluid formed leptomeningeal metastases whereas ABAT knockdown cells could not. These results suggest ABAT expression in MB cells can be modulated by the tumor microenvironment and is required to form leptomeningeal metastases.

scholarly journals Regulation of Metabolic Reprogramming by Long Non-Coding RNAs in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3485
Author(s):  
Assunta Sellitto ◽  
Giovanni Pecoraro ◽  
Giorgio Giurato ◽  
Giovanni Nassa ◽  
Francesca Rizzo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cancer Cells ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Metabolic Alterations ◽  
Cell Proliferation And Differentiation ◽  
Non Coding Rna ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Additional Level

Metabolic reprogramming is a well described hallmark of cancer. Oncogenic stimuli and the microenvironment shape the metabolic phenotype of cancer cells, causing pathological modifications of carbohydrate, amino acid and lipid metabolism that support the uncontrolled growth and proliferation of cancer cells. Conversely, metabolic alterations in cancer can drive changes in genetic programs affecting cell proliferation and differentiation. In recent years, the role of non-coding RNAs in metabolic reprogramming in cancer has been extensively studied. Here, we review this topic, with a focus on glucose, glutamine, and lipid metabolism and point to some evidence that metabolic alterations occurring in cancer can drive changes in non-coding RNA expression, thus adding an additional level of complexity in the relationship between metabolism and genetic programs in cancer cells.

Human pancreatic ribonuclease 1

Cancer ◽  
2000 ◽  
Vol 89 (6) ◽  
pp. 1252-1258 ◽  
Author(s):  
Rosa Peracaula ◽  
Karen R. Cleary ◽  
Julia Lorenzo ◽  
Rafael de Llorens ◽  
Marsha L. Frazier
Keyword(s):  
Pancreatic Ribonuclease ◽  
Human Pancreatic Ribonuclease

scholarly journals Hypoxia and the metabolic phenotype of prostate cancer cells

2009 ◽  
Vol 1787 (12) ◽  
pp. 1433-1443 ◽  
Author(s):  
L.H. Higgins ◽  
H.G. Withers ◽  
A. Garbens ◽  
H.D. Love ◽  
L. Magnoni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Metabolic Phenotype ◽  
Prostate Cancer Cells

scholarly journals Metabolic plasticity imparts erlotinib-resistance in pancreatic cancer by upregulating glucose-6-phosphate dehydrogenase

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Neha Sharma ◽  
Alok Bhushan ◽  
Jun He ◽  
Gagan Kaushal ◽  
Vikas Bhardwaj
Keyword(s):  
Pancreatic Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Treatment Options ◽  
Pentose Phosphate ◽  
Metabolic Phenotype ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Resistant Cells

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant forms of cancer. Lack of effective treatment options and drug resistance contributes to the low survival among PDAC patients. In this study, we investigated the metabolic alterations in pancreatic cancer cells that do not respond to the EGFR inhibitor erlotinib. We selected erlotinib-resistant pancreatic cancer cells from MiaPaCa2 and AsPC1 cell lines. Metabolic profiling of erlotinib-resistant cells revealed a significant downregulation of glycolytic activity and reduced level of glycolytic metabolites compared to the sensitive cells. The resistant cells displayed elevated expression of the pentose phosphate pathway (PPP) enzymes involved in ROS regulation and nucleotide biosynthesis. The enhanced PPP elevated cellular NADPH/NADP+ ratio and protected the cells from reactive oxygen species (ROS)-induced damage. Inhibition of PPP using 6-aminonicotinamide (6AN) elevated ROS levels, induced G1 cell cycle arrest, and sensitized resistant cells to erlotinib. Genetic studies identified elevated PPP enzyme glucose-6-phosphate dehydrogenase (G6PD) as an important contributor to erlotinib resistance. Mechanistically, our data showed that upregulation of inhibitor of differentiation (ID1) regulates G6PD expression in resistant cells thus contributing to altered metabolic phenotype and reduced response to erlotinib. Together, our results highlight an underlying role of tumor metabolism in PDAC drug response and identify G6PD as a target to overcome drug resistance.

scholarly journals Metabolism-Based Molecular Sub-Phenotyping Predict Ketogenic Diet Responses in Colorectal Cancer

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 356-356
Author(s):  
Meng Tang ◽  
Qi Zhang ◽  
Kangping Zhang ◽  
Xi Zhang ◽  
Hanping Shi
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Ketogenic Diet ◽  
Theoretical Basis ◽  
Nutritional Stress ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Colon Cancer Cells ◽  
Metabolic Heterogeneity

Abstract Objectives Current studies have confirmed that the sensitivity of the ketogenic diet (KD) therapy for cancer depends on the low expression of ketolytic enzymes. However, increasing evidence showed that heterogeneity of tumor metabolism leads to inconsistent efficacies of KD therapy, which broke the illusion of the possibility of cancer treatment. Our study aims to construct colon cancer metabolism-related molecular subtyping. Furthermore, to explore the metabolic heterogeneity in diverse colon cancer cells and illuminate the mechanisms of mitochondrial metabolic reprogramming. Thus, providing a theoretical basis for clinical nutritional therapy and combined intervention measures based on metabolic molecular phenotyping. Methods We selected 19 genes associated with glucose and the keto-body metabolic pathway, then constructed a prognostic gene signature by LASSO and KM curve.  Based on the screened metabolic molecules, we further explored the nutrition metabolic heterogeneity and illuminate our understanding of mitochondrial metabolic reprogramming under nutritional stress in vivo. Results Through the integration of patients’ transcriptomics data,  we stratified colon cancer patients into three significant phenotypes with distinct glycolytic and ketolytic characteristics. We identified glycolysis + subtype with either GLUT1 or PFKFB3 overexpression, and ketolysis + subtype with either OXCT1 or ACAT1 deficiency.  In general, combining glycolysis+/ketolysis-phenotype demonstrated the worst prognosis. Furthermore, we discovered the metabolic heterogeneity through western blot and energy metabolic phenotype analysis which also confirmed that these different colon cancer cells showed great significance in metabolic reprogramming under nutritional stress. Conclusions The multi-target combination of metabolic phenotyping proved to be a foundation for individualized molecular stratified treatment which plays an essential role in predicting effectiveness of nutritional modulation therapy among colon cancer patients. It provided a theoretical basis for the clinical trial of KD therapy for patients with specific metabolic subtypes of colon cancer. Funding Sources The National Key Research and Development Program: The key technology of palliative care and nursing for cancer patients.

A Nuclear Localization Sequence Endows Human Pancreatic Ribonuclease with Cytotoxic Activity†

Biochemistry ◽  
2004 ◽  
Vol 43 (8) ◽  
pp. 2167-2177 ◽  
Author(s):  
Montserrat Bosch ◽  
Antoni Benito ◽  
Marc Ribó ◽  
Teresa Puig ◽  
Bruno Beaumelle ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Nuclear Localization ◽  
Nuclear Localization Sequence ◽  
Pancreatic Ribonuclease ◽  
Localization Sequence ◽  
Human Pancreatic Ribonuclease

scholarly journals Inhibition of Human Pancreatic Ribonuclease by the Human Ribonuclease Inhibitor Protein

2007 ◽  
Vol 368 (2) ◽  
pp. 434-449 ◽  
Author(s):  
R. Jeremy Johnson ◽  
Jason G. McCoy ◽  
Craig A. Bingman ◽  
George N. Phillips ◽  
Ronald T. Raines
Keyword(s):  
Inhibitor Protein ◽  
Ribonuclease Inhibitor ◽  
Pancreatic Ribonuclease ◽  
Human Pancreatic Ribonuclease
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