scholarly journals Vacuolar H+-ATPase Subunit V0C Regulates Aerobic Glycolysis of Esophageal Cancer Cells via PKM2 Signaling

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1137 ◽  
Author(s):  
Sung Wook Son ◽  
Gia Cac Chau ◽  
Seong-Tae Kim ◽  
Sung Hee Um
Keyword(s):  
Esophageal Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Aerobic Glycolysis ◽  
Glycolytic Enzyme ◽  
Ph Homeostasis ◽  
Atpase Subunit ◽  
Esophageal Cancer Cells

The vacuolar H+-adenosine triphosphatase (ATPase) subunit V0C (ATP6V0C), a proton-conducting, pore-forming subunit of vacuolar ATPase, maintains pH homeostasis and induces organelle acidification. The intracellular and extracellular pH of cancer cells affects their growth; however, the role of ATP6V0C in highly invasive esophageal cancer cells (ECCs) remains unclear. In this study, we examined the role of ATP6V0C in glucose metabolism in ECCs. The ATP6V0C depletion attenuated ECC proliferation, invasion, and suppressed glucose metabolism, as indicated by reduced glucose uptake and decreased lactate and adenosine triphosphate (ATP) production in cells. Consistent with this, expression of glycolytic enzyme and the extracellular acidification rate (ECAR) were also decreased by ATP6V0C knockdown. Mechanistically, ATP6V0C interacted with pyruvate kinase isoform M2 (PKM2), a key regulator of glycolysis in ECCs. The ATP6V0C depletion reduced PKM2 phosphorylation at tyrosine residue 105 (Tyr105), leading to inhibition of nuclear translocation of PKM2. In addition, ATP6V0C was recruited at hypoxia response element (HRE) sites in the lactate dehydrogenase A (LDHA) gene for glycolysis. Thus, our data suggest that ATP6V0C enhances aerobic glycolysis and motility in ECCs.

scholarly journals Evolved resistance to GAPDH inhibition results in loss of the Warburg Effect but retains a different state of glycolysis

2019 ◽  
Author(s):  
Maria V. Liberti ◽  
Annamarie E. Allen ◽  
Vijyendra Ramesh ◽  
Ziwei Dai ◽  
Katherine R. Singleton ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Warburg Effect ◽  
Acid Metabolism ◽  
Aerobic Glycolysis ◽  
Specific Inhibitor ◽  
Central Carbon Metabolism ◽  
Glycolytic Enzyme ◽  
Altered State ◽  
The Warburg Effect

SUMMARYAerobic glycolysis or the Warburg Effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although ubiquitous, the biological role of the WE remains controversial and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, we evolved resistance to koningic acid (KA), a natural product shown to be a specific inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme during the WE. We find that KA-resistant cells lose the WE but conduct glycolysis and surprisingly remain dependent on glucose and central carbon metabolism. Consequentially this altered state of glycolysis leads to differential metabolic activity and requirements including emergent activities in and dependencies on fatty acid metabolism. Together, these findings reveal that, contrary to some recent reports, aerobic glycolysis is a functionally distinct entity from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.

scholarly journals TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Fanglong Wu ◽  
Shimeng Wang ◽  
Qingxiang Zeng ◽  
Junjiang Liu ◽  
Jin Yang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Oral Cancer ◽  
Nuclear Translocation ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Metabolic Reprogramming ◽  
Cancer Associated Fibroblasts

AbstractCancer-associated fibroblasts (CAFs) are highly heterogeneous and differentiated stromal cells that promote tumor progression via remodeling of extracellular matrix, maintenance of stemness, angiogenesis, and modulation of tumor metabolism. Aerobic glycolysis is characterized by an increased uptake of glucose for conversion into lactate under sufficient oxygen conditions, and this metabolic process occurs at the site of energy exchange between CAFs and cancer cells. As a hallmark of cancer, metabolic reprogramming of CAFs is defined as reverse Warburg effect (RWE), characterized by increased lactate, glutamine, and pyruvate, etc. derived from aerobic glycolysis. Given that the TGF-β signal cascade plays a critical role in RWE mainly through metabolic reprogramming related proteins including pyruvate kinase muscle isozyme 2 (PKM2), however, the role of nuclear PKM2 in modifying glycolysis remains largely unknown. In this study, using a series of in vitro and in vivo experiments, we provide evidence that TGF-βRII overexpression suppresses glucose metabolism in CAFs by attenuating PKM2 nuclear translocation, thereby inhibiting oral cancer tumor growth. This study highlights a novel pathway that explains the role of TGF-βRII in CAFs glucose metabolism and suggests that targeting TGF-βRII in CAFs might represent a therapeutic approach for oral cancer.

scholarly journals LncRNA MAGI2-AS3 Overexpression Sensitizes Esophageal Cancer Cells to Irradiation Through Down-Regulation of HOXB7 via EZH2

2020 ◽  
Vol 8 ◽  
Author(s):  
Wenfang Cheng ◽  
Xiuling Shi ◽  
Mingqiang Lin ◽  
Qiwei Yao ◽  
Jiayu Ma ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Potential Role ◽  
Luciferase Reporter ◽  
Cancer Resistance ◽  
Down Regulation ◽  
Aberrant Expression ◽  
Gene Assay ◽  
Esophageal Cancer Cells

BackgroundAccumulating evidence has suggested that aberrant expression of long non-coding RNAs (lncRNAs) may contribute to cancer progression in association with radioresistance. The current study aimed to identify the potential role of lncRNA MAGI2-AS3 and the underlying mechanism in its regulation of the radio-sensitivity of esophageal cancer cells.Methods and ResultsInitially, we detected high expression of HOXB7 from microarray-based gene expression profiling of esophageal cancer. Then, we identified the interactions among MAGI2-AS3, HOXB7, and EZH2 by dual-luciferase reporter gene assay, RNA pull-down assay, RIP assay and ChIP assay. HOXB7 was highly-expressed, while MAGI2-AS3 was poorly-expressed in esophageal cancer tissues and cells. The effect of MAGI2-AS3 and HOXB7 on esophageal cancer cell proliferation and apoptosis as well as tumorigenicity of radioresistant cells was examined by gain- and loss-of-function experiments. Interestingly, MAGI2-AS3 down-regulated HOXB7 through interaction with EZH2, which promoted cell apoptosis and inhibited proliferation and radio-resistance. Besides, down-regulation of MAGI2-AS3 exerted a promoting effect on these malignant phenotypes.ConclusionTaken together, our results reveal the potential role of MAGI2-AS3 over-expression in controlling esophageal cancer resistance to radiotherapy by down-regulating HOXB7, this providing a candidate biomarker for resistance to radiotherapy.

scholarly journals Pterostilbene Inhibits the Growth of Human Esophageal Cancer Cells by Regulating Endoplasmic Reticulum Stress

2016 ◽  
Vol 38 (3) ◽  
pp. 1226-1244 ◽  
Author(s):  
Yingtong Feng ◽  
Yang Yang ◽  
Chongxi Fan ◽  
Shouyin Di ◽  
Wei Hu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Apoptotic Index ◽  
Related Protein ◽  
Apoptosis Related Protein ◽  
Human Esophageal Cancer ◽  
Esophageal Cancer Cells

Background/Aims: Pterostilbene (PTE), a natural dimethylated resveratrol analog from blueberries, is known to have diverse pharmacological activities, including anticancer properties. In this study, we investigated the anticancer activity of PTE against human esophageal cancer cells both in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process. Methods: Cell viability, the apoptotic index, Caspase 3 activity, adhesion, migration, reactive oxygen species (ROS) levels, and glutathione (GSH) levels were detected to explore the effect of PTE on human EC109 esophageal cancer cells. Furthermore, siRNA transfection and a chemical inhibitor were employed to confirm the role of ERS. Results: PTE treatment dose- and time-dependently decreased the viability of human esophageal cancer EC109 cells. PTE also decreased tumor cell adhesion, migration and intracellular GSH levels while increasing the apoptotic index, Caspase 3 activity and ROS levels, which suggest the strong anticancer activity of PTE. Furthermore, PTE treatment increased the expression of ERS-related molecules (GRP78, ATF6, p-PERK, p-eIF2α and CHOP), upregulated the pro-apoptosis-related protein PUMA and downregulated the anti-apoptosis-related protein Bcl-2 while promoting the translocation of cytochrome c from mitochondria to cytosol and the activation of Caspase 9 and Caspase 12. The downregulation of ERS signaling by CHOP siRNA desensitized esophageal cancer cells to PTE treatment, whereas upregulation of ERS signaling by thapsigargin (THA) had the opposite effect. N-Acetylcysteine (NAC), a ROS scavenger, also desensitized esophageal cancer cells to PTE treatment. Conclusions: Overall, the results indicate that PTE is a potent anti-cancer pharmaceutical against human esophageal cancer, and the possible mechanism involves the activation of ERS signaling pathways.

scholarly journals X-linked inhibitor of apoptosis protein accelerates migration by inducing epithelial–mesenchymal transition through TGF-β signaling pathway in esophageal cancer cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuxiang Jin ◽  
Xinye Lu ◽  
Mingdong Wang ◽  
Xuewei Zhao ◽  
Lei Xue
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitor Of Apoptosis ◽  
Mesenchymal Transition ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Esophageal Cancer Cells ◽  
Emt Markers

Abstract Background The prognosis of esophageal cancer is still dismal because of its high probability of metastasis that is likely related to the cellular process of epithelial–mesenchymal transition (EMT). Recent studies have shown a novel role of X-linked inhibitor of apoptosis protein (XIAP) in regulating the migration process of cancer cells and, therefore, linking to progression and poor prognosis of cancer. Methods The expression of XIAP in esophageal squamous cell cancer (ESCC) tissues was determined by immunohistochemistry assay. Cell migration was analyzed by wound healing assay and Transwell assay. The expression of EMT markers (E-cadherin, N-cadherin and Vimentin) was revealed by immunofluorescence assay. Quantitative real‑time PCR analysis and Western blot analysis were used to detect the expression of XIAP and EMT markers as well as transforming growth factor-β (TGF-β) at mRNA and protein level, respectively. Results We found that the expression of XIAP closely correlated to the probability of lymphatic metastasis in patients and that ESCC patients with the high XIAP expression were associated with worse overall survival (OS). Univariate and multivariate analysis also revealed XIAP as an independent prognostic factor for overall survival in ESCC patients. In both EC9706 and TE13 cell lines, knockdown of XIAP decreased the migration of cancer cells by inhibiting EMT process through regulating the TGF-β signaling pathway, pinpointing a regulatory role of XIAP in migratory process upon TGF-β activation. Conclusions Taken together, our results suggest XIAP as a important prognostic and regulative factor in ESCC patients. XIAP may promote migration of esophageal cancer cells through the activation of TGF-β mediated EMT.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

scholarly journals Characteristics of P-Type and N-Type Photoelectrochemical Biosensors: A Case Study for Esophageal Cancer Detection

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1065
Author(s):  
Joseph-Hang Leung ◽  
Hong-Thai Nguyen ◽  
Shih-Wei Feng ◽  
Sofya B. Artemkina ◽  
Vladimir E. Fedorov ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Carrier Transport ◽  
X Ray Diffraction ◽  
Photoelectrochemical Response ◽  
Carrier Separation ◽  
Human Esophageal Cancer ◽  
P Type ◽  
Esophageal Cancer Cells

P-type and N-type photoelectrochemical (PEC) biosensors were established in the laboratory to discuss the correlation between characteristic substances and photoactive material properties through the photogenerated charge carrier transport mechanism. Four types of human esophageal cancer cells (ECCs) were analyzed without requiring additional bias voltage. Photoelectrical characteristics were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), UV–vis reflectance spectroscopy, and photocurrent response analyses. Results showed that smaller photocurrent was measured in cases with advanced cancer stages. Glutathione (L-glutathione reduced, GSH) and Glutathione disulfide (GSSG) in cancer cells carry out redox reactions during carrier separation, which changes the photocurrent. The sensor can identify ECC stages with a certain level of photoelectrochemical response. The detection error can be optimized by adjusting the number of cells, and the detection time of about 5 min allowed repeated measurement.

scholarly journals Inhibition of pRB Pathway Differentially Modulates Apoptosis in Esophageal Cancer Cells

2017 ◽  
Vol 10 (5) ◽  
pp. 726-733 ◽  
Author(s):  
Rossana C. Soletti ◽  
Deborah Biasoli ◽  
Nathassya A.L.V. Rodrigues ◽  
João M.A. Delou ◽  
Renata Maciel ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Esophageal Cancer Cells
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