Expression of AGPAT2, an enzyme involved in the glycerophospholipid/triacylglycerol biosynthesis pathway, is directly regulated by HIF-1 and promotes survival and etoposide resistance of cancer cells under hypoxia

2018 ◽  
Vol 1863 (9) ◽  
pp. 1142-1152 ◽  
Author(s):  
Eleni-Anastasia Triantafyllou ◽  
Eleni Georgatsou ◽  
Ilias Mylonis ◽  
George Simos ◽  
Efrosyni Paraskeva
Keyword(s):  
Cancer Cells ◽  
Biosynthesis Pathway ◽  
Triacylglycerol Biosynthesis

scholarly journals Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer

2020 ◽  
Vol 117 (51) ◽  
pp. 32433-32442
Author(s):  
Ji-Yoon Lee ◽  
Miso Nam ◽  
Hye Young Son ◽  
Kwangbeom Hyun ◽  
Seo Young Jang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Polyunsaturated Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Intestinal Type ◽  
Biosynthesis Pathway ◽  
Gastric Cancer Cells ◽  
Regulated Necrosis

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.

scholarly journals Cysteine catabolism and the serine biosynthesis pathway support pyruvate production during pyruvate kinase knockdown in pancreatic cancer cells

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Lei Yu ◽  
Shao Thing Teoh ◽  
Elliot Ensink ◽  
Martin P. Ogrodzinski ◽  
Che Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Metabolic Pathways ◽  
Treatment Options ◽  
Ductal Adenocarcinoma ◽  
Metabolic Enzyme ◽  
Biosynthesis Pathway ◽  
Pancreatic Cancer Cells ◽  
Serine Biosynthesis

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options. Pyruvate kinase, especially the M2 isoform (PKM2), is highly expressed in PDAC cells, but its role in pancreatic cancer remains controversial. To investigate the role of pyruvate kinase in pancreatic cancer, we knocked down PKM2 individually as well as both PKM1 and PKM2 concurrently (PKM1/2) in cell lines derived from a KrasG12D/-; p53-/- pancreatic mouse model. Methods We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine metabolic profiles of wildtype and PKM1/2 knockdown PDAC cells. We further used stable isotope-labeled metabolic precursors and LC-MS/MS to determine metabolic pathways upregulated in PKM1/2 knockdown cells. We then targeted metabolic pathways upregulated in PKM1/2 knockdown cells using CRISPR/Cas9 gene editing technology. Results PDAC cells are able to proliferate and continue to produce pyruvate despite PKM1/2 knockdown. The serine biosynthesis pathway partially contributed to pyruvate production during PKM1/2 knockdown: knockout of phosphoglycerate dehydrogenase in this pathway decreased pyruvate production from glucose. In addition, cysteine catabolism generated ~ 20% of intracellular pyruvate in PDAC cells. Other potential sources of pyruvate include the sialic acid pathway and catabolism of glutamine, serine, tryptophan, and threonine. However, these sources did not provide significant levels of pyruvate in PKM1/2 knockdown cells. Conclusion PKM1/2 knockdown does not impact the proliferation of pancreatic cancer cells. The serine biosynthesis pathway supports conversion of glucose to pyruvate during pyruvate kinase knockdown. However, direct conversion of serine to pyruvate was not observed during PKM1/2 knockdown. Investigating several alternative sources of pyruvate identified cysteine catabolism for pyruvate production during PKM1/2 knockdown. Surprisingly, we find that a large percentage of intracellular pyruvate comes from cysteine. Our results highlight the ability of PDAC cells to adaptively rewire their metabolic pathways during knockdown of a key metabolic enzyme.

Identification and expression analysis of castor bean (Ricinus communis) genes encoding enzymes from the triacylglycerol biosynthesis pathway

Plant Science ◽  
2010 ◽  
Vol 179 (5) ◽  
pp. 499-509 ◽  
Author(s):  
Alexandro Cagliari ◽  
Márcia Margis-Pinheiro ◽  
Guilherme Loss ◽  
Alexandra Antunes Mastroberti ◽  
Jorge Ernesto de Araujo Mariath ◽  
...  
Keyword(s):  
Expression Analysis ◽  
Castor Bean ◽  
Ricinus Communis ◽  
Biosynthesis Pathway ◽  
Triacylglycerol Biosynthesis ◽  
Genes Encoding

scholarly journals α-Linolenic acid suppresses cholesterol and triacylglycerol biosynthesis pathway by suppressing SREBP-2, SREBP-1a and -1c expression

2012 ◽  
Vol 65 (6) ◽  
pp. 899-907 ◽  
Author(s):  
Satoshi Fukumitsu ◽  
Myra O. Villareal ◽  
Shoko Onaga ◽  
Kazuhiko Aida ◽  
Junkyu Han ◽  
...  
Keyword(s):  
Linolenic Acid ◽  
Biosynthesis Pathway ◽  
Triacylglycerol Biosynthesis

Studies on triacylglycerol biosynthesis pathway in the insect Rhodnius prolixus

2011 ◽  
Vol 164 ◽  
pp. S29
Author(s):  
Michele Alves-Bezerra ◽  
Clarissa M. Maya-Monteiro ◽  
Katia C. Gondim
Keyword(s):  
Rhodnius Prolixus ◽  
Biosynthesis Pathway ◽  
Triacylglycerol Biosynthesis

Ultrastructural modification of cellular interactions in cancer tumor

1978 ◽  
Vol 36 (2) ◽  
pp. 318-319
Author(s):  
N. P. Dmitrieva
Keyword(s):  
Cancer Cells ◽  
Human Thyroid ◽  
Adjacent Cell ◽  
Main Role ◽  
Cellular Interactions ◽  
Electron Microscopic ◽  
Cancer Tumor ◽  
Normal Human ◽  
Characteristic Features

One of the most characteristic features of cancer cells is their ability to metastasia. It is suggested that the modifications of the structure and properties of cancer cells surfaces play the main role in this process. The present work was aimed at finding out what ultrastructural features apear in tumor in vivo which removal of individual cancer cells from the cell population can provide. For this purpose the cellular interactions in the normal human thyroid and cancer tumor of this gland electron microscopic were studied. The tissues were fixed in osmium tetroxide and were embedded in Araldite-Epon.In normal human thyroid the most common type of intercellular contacts was represented by simple junction formed by the parallelalignment of adjacent cell membranees leaving in between an intermembranes space 15-20 nm filled with electronlucid material (Fig. 1a). Sometimes in the basal part of cells dilatations of the intercellular space 40-50 nm wide were found (Fig. 1a). Here the cell surfaces may form single short microvilli.

Ultrastructural Localization Study of Carcinoembryonic Antigen (CEA) in Gastric Cancer: Immunoelectron Microscopic Observation

1990 ◽  
Vol 48 (3) ◽  
pp. 252-253
Author(s):  
Dong Yuming ◽  
Yang Guanglin ◽  
Wu Jifeng ◽  
Chen Xiaolin
Keyword(s):  
Gastric Cancer ◽  
Intestinal Metaplasia ◽  
Cancer Cells ◽  
Microscopic Observation ◽  
Biological Significance ◽  
Ultrastructural Localization ◽  
Mucinous Carcinoma ◽  
Surface Glycoprotein ◽  
Tubular Adenocarcinoma ◽  
Pap Method

On the basis of light microscopic observation, the ultrastructural localization of CEA in gastric cancer was studied by immunoelectron microscopic technique. The distribution of CEA in gastric cancer and its biological significance and the mechanism of abnormal distribution of CEA were further discussed.Among 104 surgically resected specimens of gastric cancer with PAP method at light microscopic level, the incidence of CEA(+) was 85.58%. All of mucinous carcinoma exhibited CEA(+). In tubular adenocarcinoma the incidence of CEA(+) showed a tendency to rising with the increase of degree of differentiation. In normal epithelia and intestinal metaplasia CEA was faintly present and was found only in the luminal surface. The CEA staining patterns in cancer cells were of three types--- cytoplasmic, membranous and weak reactive type. The ultrastructural localization of CEA in 14 cases of gastric cancer was studied by immunoelectron microscopic technique.There was a little or no CEA in the microvilli of normal epithelia. In intestinal metaplasia CEA was found on the microvilli of absorptive cells and among the mucus particles of goblet cells. In gastric cancer CEA was also distributed on the lateral and basal surface or even over the entire surface of cancer cells and lost their polarity completely. Many studies had proved that the alterations in surface glycoprotein were characteristic changes of tumor cells. The antigenic determinant of CEA was glycoprotein, so the alterations of tumor-associated surface glycoprotein opened up a new way for the diagnosis of tumors.

Sign in / Sign up

Export Citation Format

Share Document