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https://www.readbyqxmd.com/read/29349661/pkm2-is-involved-in-neuropathic-pain-by-regulating-erk-and-stat3-activation-in-rat-spinal-cord
#1
Binbin Wang, Siyuan Liu, Bingbing Fan, Xingguo Xu, Yonglin Chen, Rongxiang Lu, Zhongling Xu, Xiaojuan Liu
BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis...
January 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29344170/phosphorylation-of-ser6-in-hnrnpa1-by-s6k2-regulates-glucose-metabolism-and-cell-growth-in-colorectal-cancer
#2
Yan Sun, Man Luo, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao, Yu Hu
Abnormal glucose metabolism is critical in colorectal cancer (CRC) development. Expression of the pyruvate kinase (PK) M2 isoform, rather than the PKM1 isoform, serves important functions in reprogramming the glucose metabolism of cancer cells. Preferential expression of PKM2 is primarily driven by alternative splicing, which is coordinated by a group of splicing factors including heterogeneous nuclear ribonucleoprotein (hnRNP)A1, hnRNPA2 and RNA binding motif containing. However, the underlying molecular mechanisms associated with cancer cell expression of PKM2, instead of PKM1, remain unknown...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343208/lapatinib-inhibits-breast-cancer-cell-proliferation-by-influencing-pkm2-expression
#3
Mingxiu Guan, Yingna Tong, Minghua Guan, Xiaobin Liu, Meng Wang, Ruifang Niu, Fei Zhang, Dong Dong, Jie Shao, Yunli Zhou
Pyruvate kinase type M2, which is expressed in multiple tumor cell types and plays a key role in aerobic glycolysis, also has nonglycolytic functions and can regulate transcription and cell proliferation. The results of this study show that epidermal growth factor receptor activation induces pyruvate kinase type M2 nuclear translocation. To further determine the relationship between pyruvate kinase type M2 and epidermal growth factor receptor, we analyzed pathological data from mammary glands and performed epidermal growth factor receptor/human epidermal growth factor receptor 2 knockdown to reveal that pyruvate kinase type M2 is associated with epidermal growth factor receptor and human epidermal growth factor receptor 2...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29340090/high-glucose-enhances-the-metastatic-potential-of-tongue-squamous-cell-carcinoma-via-the-pkm2-pathway
#4
Wei Wang, Qianting He, Wangxiang Yan, Jingjing Sun, Zujian Chen, Zhonghua Liu, Zhiyuan Lu, Jinsong Hou, Yisen Shao, Xiaofeng Zhou, Anxun Wang
Previous evidence has indicated an increased cancer risk in individuals with diabetes mellitus (DM). The aim of this study was to investigate the relationship between DM (high glucose) and tongue squamous cell carcinoma (TSCC) and how high glucose mediated the metastatic potential of TSCC. The relationship between DM and TSCC was assessed in a retrospective study. The role and its mechanism of high glucose on the proliferation, metastatic potential of TSCC were investigated in vitro and in vivo. The prevalence rate of DM in patients with TSCC was 12...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29335522/pyruvate-kinase-m2-promotes-pancreatic-ductal-adenocarcinoma-invasion-and-metastasis-through-phosphorylation-and-stabilization-of-pak2-protein
#5
Tsu-Yao Cheng, Yi-Chieh Yang, Hsiu-Po Wang, Yu-Wen Tien, Chia-Tung Shun, Hsin-Yi Huang, Michael Hsiao, Kuo-Tai Hua
Pyruvate kinase muscle isozymes (PKMs) have crucial roles in regulating metabolic changes during carcinogenesis. A switch from PKM1 to PKM2 isoform was thought to lead to aerobic glycolysis promoting carcinogenesis, and was considered as one of the cancer signatures. However, recent evidence has argued against the existence of PKM isoform switch and related metabolic effects during cancer progression. We compared the effects of PKM1 and PKM2 in cell invasiveness and metastasis of pancreatic ductal adenocarcinoma (PDAC)...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29312595/pyruvate-kinase-m2-phosphorylates-h2ax-and-promotes-genomic-instability-in-human-tumor-cells
#6
Li Xia, Kang Qin, Xin-Ran Wang, Xiao-Ling Wang, Ai-Wu Zhou, Guo-Qiang Chen, Ying Lu
Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP, a rate-limiting reaction in glycolysis. M2 isoform of PK (PKM2) is the predominant form of PK expressed in tumors. In addition to its well established cytosolic functions as a glycolytic enzyme, PKM2 displays nuclear localization and important nonmetabolic functions in tumorigenesis. Herein, we report that nuclear PKM2 interacts with histone H2AX under DNA damage conditions. Depletion of PKM2 decreased the level of serine 139-phosphorylated H2AX (γ-H2AX) in response to DNA damage...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29303786/aerobic-glycolysis-in-amyotrophic-lateral-sclerosis-and-huntington-s-disease
#7
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Neurodegenerative cells are the sites of numerous metabolic and energetic abnormalities with abnormalities in energy production. Energy is the primary determinant of neuronal viability. In neurodegenerative cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), WNT/β-catenin pathway is upregulated. We focused this review on the hypothesis of aerobic glycolysis stimulated by the upregulation of WNT/β-catenin pathway in ALS and HD...
January 5, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29301575/warburg-effect-hypothesis-in-autism-spectrum-disorders
#8
REVIEW
Alexandre Vallée, Jean-Noël Vallée
Autism spectrum disorder (ASD) is a neurodevelopmental disease which is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. In altered cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In ASD, the canonical WNT/β-catenin pathway is upregulated. We focus this review on the hypothesis of Warburg effect stimulated by the overexpression of the canonical WNT/β-catenin pathway in ASD. Upregulation of WNT/β-catenin pathway induces aerobic glycolysis, named Warburg effect, through activation of glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactate dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH)...
January 4, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29299177/pkm2-in-carcinogenesis-and-oncotherapy
#9
REVIEW
Xia He, Suya Du, Tiantian Lei, Xiang Li, Yilong Liu, Hailian Wang, Rongsheng Tong, Yi Wang
Tumor cell metabolism is characterized by abundant glucose consumption and aerobic glycolysis. And pyruvate kinase M2 (PKM2) plays a decisive role in glycolysis, significantly contributing to the Warburg effect, tumor growth, angiogenesis, cell division, metastasis and apoptosis. To date, researchers have unraveled the potential of pyruvate kinase M2 as an antitumor target, which suggests a new orientation for oncotherapy. Herein, we focus on the role of pyruvate kinase M2 in tumor cell development and its function as a potential new therapeutic target for tumor treatment...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290767/efficacy-of-shikonin-against-esophageal-cancer-cells-and-its-possible-mechanisms-in-vitro-and-in-vivo
#10
Jian-Cai Tang, Jia Zhao, Feng Long, Jian-Ye Chen, Bo Mu, Zhen Jiang, Yonggan Ren, Jian Yang
Increasing evidences indicate that shikonin can suppress the tumor growth. However, the mechanisms remain elusive. In the present study, we investigated the effects and mechanisms of shikonin against esophageal cancer. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2 (PKM2) in esophageal cancer tissues and cells was detected by immunohistochemistry and Western blot. CCK-8 was used to examine the esophageal cancer cell viability. Apoptosis and cell cycle were analyzed by flow cytometry...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29277786/correlation-of-pyruvate-kinase-m2-expression-with-clinicopathological-data-in-ovarian-cancer
#11
Christopher Kobierzycki, Aleksandra Piotrowska, Krzysztof Latkowski, Maciej Zabel, Ewa Nowak-Markwitz, Marek Spaczynski, Witold Kedzia, Bartosz Pula, Marzenna Podhorska-Okolow, Piotr Dziegiel
BACKGROUND/AIM: It has been shown in many studies that expression of pyruvate kinase (PK) enzyme plays a key role during cellular metabolism. There is evidence that cancer cells manifesting very dynamic proliferation may control their division in various mechanisms, i.a. by expression of PKM2 isoform. The exact role of PKM2 in ovarian cancer (OC) cells and cancer associated fibroblasts (CAFs) have not been elucidated. MATERIALS AND METHODS: The present study was focused on analysis of PKM2 expression in cancer cells and CAFs in 97 OC cases, mostly of serous histological type...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29275212/nrf2-facilitates-breast-cancer-cell-growth-via-hif1%C3%A9-mediated-metabolic-reprogramming
#12
Hong-Sheng Zhang, Guang-Yuan Du, Zhong-Guo Zhang, Zhen Zhou, Hong-Liang Sun, Xiao-Ying Yu, Yu-Ting Shi, Dan-Ning Xiong, Hu Li, Ying-Hui Huang
High aerobic glycolysis not only provides energy to breast cancer cells, but also supports their anabolic growth. The redox sensitive transcription factor NRF2 is over-expressed in multiple cancers, including breast cancer. It is unclear whether NRF2 could promote breast cancer cell growth through enhancing glycolysis. In this study, we found that NRF2 and HIF1α mRNA and protein levels were significantly increased in MCF-7 and MDA-MB-231 breast cancer cells as compared to MCF-10A benign breast epithelial cells...
December 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29273328/elevation-of-serum-pyruvate-kinase-m2-pkm2-in-ibd-and-its-relationship-to-ibd-indices
#13
Ahmed A Almousa, Marc Morris, Sharyle Fowler, Jennifer Jones, Jane Alcorn
OBJECTIVES: Endoscopy remains the gold standard to diagnose and evaluate inflammatory bowel disease (IBD) activity. Current biomarkers or their combinations cannot adequately predict IBD risk, diagnosis, progression or relapse, and response to therapy. Pyruvate kinase M2 (PKM2) is emerging as a significant mediator of the inflammatory process. We aim to assess levels of serum PKM2 in healthy and newly diagnosed IBD patients and its relationship with IBD indices and microbiota changes...
December 19, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/29259242/photoreceptor-metabolic-reprogramming-provides-survival-advantage-in-acute-stress-while-causing-chronic-degeneration
#14
Thomas J Wubben, Mercy Pawar, Andrew Smith, Kevin Toolan, Heather Hager, Cagri G Besirli
Photoreceptor death is the root cause of vision loss in many retinal disorders, and there is an unmet need for neuroprotective modalities to improve photoreceptor survival. The biosynthetic requirement of photoreceptors is among the highest in the body, and to meet this demand, photoreceptors maintain their ability to perform aerobic glycolysis. This highly regulated form of glycolysis allows cells to efficiently budget their metabolic needs and may be a critical link between photoreceptor function and survival...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229835/o-glcnacylation-destabilizes-the-active-tetrameric-pkm2-to-promote-the-warburg-effect
#15
Yang Wang, Jia Liu, Xin Jin, Dapeng Zhang, Dongxue Li, Fengqi Hao, Yunpeng Feng, Shan Gu, Fanlin Meng, Miaomiao Tian, Yi Zheng, Ling Xin, Xinbo Zhang, Xue Han, L Aravind, Min Wei
The Warburg effect, characterized by increased glucose uptake and lactate production, is a well-known universal across cancer cells and other proliferating cells. PKM2, a splice isoform of the pyruvate kinase (PK) specifically expressed in these cells, serves as a major regulator of this metabolic reprogramming with an adjustable activity subjected to numerous allosteric effectors and posttranslational modifications. Here, we have identified a posttranslational modification on PKM2, O-GlcNAcylation, which specifically targets Thr405 and Ser406, residues of the region encoded by the alternatively spliced exon 10 in cancer cells...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29225125/interdependence-of-glo-i-and-pkm2-in-the-metabolic-shift-to-escape-apoptosis-in-glo-i-dependent-cancer-cells
#16
Nami Shimada, Ryoko Takasawa, Sei-Ichi Tanuma
Many cancer cells undergo metabolic reprogramming known as the Warburg effect, which is characterized by a greater dependence on glycolysis for ATP generation, even under normoxic conditions. Glyoxalase I (GLO I) is a rate-limiting enzyme involved in the detoxification of cytotoxic methylglyoxal formed in glycolysis and which is known to be highly expressed in many cancer cells. Thus, specific inhibitors of GLO I are expected to be effective anticancer drugs. We previously discovered a novel GLO I inhibitor named TLSC702...
December 8, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29214019/pkm2-is-not-required-for-colon-cancer-initiated-by-apc-loss
#17
Allison N Lau, William J Israelsen, Jatin Roper, Mark J Sinnamon, Larissa Georgeon, Talya L Dayton, Alissandra L Hillis, Omer H Yilmaz, Dolores Di Vizio, Kenneth E Hung, Matthew G Vander Heiden
Background: Cancer cells express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2). PKM2 expression is not required for some cancers, and PKM2 loss can promote cancer progression; however, PKM2 has been reported to be essential in other tumor contexts, including a proposed non-metabolic role in β-catenin nuclear translocation. PKM2 is expressed in colon cancers where loss of the Apc tumor suppressor results in β-catenin nuclear translocation and aberrant activation of the canonical Wnt signaling pathway...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/29207616/pkm2-activation-sensitizes-cancer-cells-to-growth-inhibition-by-2-deoxy-d-glucose
#18
Sui Seng Tee, Jae Mo Park, Ralph E Hurd, Kyle R Brimacombe, Matthew B Boxer, Tarik F Massoud, Brian K Rutt, Daniel M Spielman
Cancer metabolism has emerged as an increasingly attractive target for interfering with tumor growth. Small molecule activators of pyruvate kinase isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in increased glucose consumption, providing the rationale for combining PKM2 activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination treatment resulted in reduced viability of a range of cell lines in standard cell culture conditions at concentrations of drugs that had no effect when used alone...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29200969/inhibition-of-breast-cancer-cell-proliferation-and-tumorigenesis-by-long-non-coding-rna-rpph1-down-regulation-of-mir-122-expression
#19
Yi Zhang, Lili Tang
Background: Recent studies showed that long non-coding RNA (lncRNA) plays an important role in many life activities. RPPH1 is one of the lncRNA genes that are expressed differently between breast cancer and normal tissues by the lncRNA gene chip. Our study was conducted to examine the regulation of lncRNA RPPH1 in breast cancer. Methods: Two cell lines, MCF-7 and MDA-MB-231, were selected to be the research objects in this study; RPPH1 overexpression and knockdown models were established by transforming vectors...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29185365/synthesis-and-antitumor-activity-of-novel-2-3-didithiocarbamate-substituted-naphthoquinones-as-inhibitors-of-pyruvate-kinase-m2-isoform
#20
Xianling Ning, Hailong Qi, Ridong Li, Yan Jin, Michael A McNutt, Yuxin Yin
The M2 isoform of pyruvate kinase (PKM2) is a potential antitumor therapeutic target. In this study, we designed and synthesised a series of 2, 3-didithiocarbamate substituted naphthoquinones as PKM2 inhibitors based on the lead compound 3k that we previously reported. Among them, compound 3f (IC50 = 1.05 ± 0.17 µM) and 3h (IC50 = 0.96 ± 0.18 µM) exhibited potent inhibition of PKM2, and their inhibitory activities are superior to compound 3k (IC50 = 2.95 ± 0.53 µM) and the known PKM2 inhibitor shikonin (IC50 = 8...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
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