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PKM2

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https://www.readbyqxmd.com/read/28802581/pkm2-aggravates-palmitate-induced-insulin-resistance-in-hepg2-cells-via-stat3-pathway
#1
Ling Chen, Zhuqi Tang, Xiaohua Wang, Hong Ma, Dandan Shan, Shiwei Cui
Studies have identified that PKM2 is related to the development of glucose intolerance and insulin resistance in rodents and humans. However, the underlying mechanism remains largely unknown. In the present study, we found that PKM2 expression was significantly elevated in insulin-resistant hepatic tissues and hepatocytes, implicating an association between PKM2 expression and hepatic insulin resistance (IR). In vitro study revealed that overexpression of PKM2 impaired the insulin signaling pathway by decreasing the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK3β)...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28791350/prl-3-improves-colorectal-cancer-cell-proliferation-and-invasion-through-il-8-mediated-glycolysis-metabolism
#2
Heyang Xu, Yujie Zeng, Lu Liu, Qian Gao, Shaowen Jin, Qiusheng Lan, Wei Lai, Xingxi Luo, Heng Wu, Yongliang Huang, Zhonghua Chu
Phosphatase of regenerating liver-3 (PRL-3) has been found to be overexpressed in liver metastases of colorectal cancer and rarely expressed in primary tumors, which plays an important role in the metastasis of colorectal cancer cells. Metabolism reprogramming has been found to be a hallmark of cancer cells, and aerobic glycolysis is a metabolic adaption for cancer cells and promotes cell proliferation. However, the association between PRL-3 and glycolysis in colorectal cancer cells is not well understood. In the present study, we explored the association between PRL-3 and glycolysis...
August 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28778087/pkm2-activation-sensitizes-cancer-cells-to-growth-inhibition-by-2-deoxy-d-glucose
#3
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...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28769740/discovery-and-validation-of-a-colorectal-cancer-classifier-in-a-new-blood-test-with-improved-performance-for-high-risk-subjects
#4
Lisa J Croner, Roslyn Dillon, Athit Kao, Stefanie N Kairs, Ryan Benz, Ib J Christensen, Hans J Nielsen, John E Blume, Bruce Wilcox
BACKGROUND: The aim was to improve upon an existing blood-based colorectal cancer (CRC) test directed to high-risk symptomatic patients, by developing a new CRC classifier to be used with a new test embodiment. The new test uses a robust assay format-electrochemiluminescence immunoassays-to quantify protein concentrations. The aim was achieved by building and validating a CRC classifier using concentration measures from a large sample set representing a true intent-to-test (ITT) symptomatic population...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28757909/metabolic-reprogramming-autophagy-and-reactive-oxygen-species-are-necessary-for-primordial-germ-cell-reprogramming-into-pluripotency
#5
D Sainz de la Maza, A Moratilla, V Aparicio, C Lorca, Y Alcaina, D Martín, M P De Miguel
Cellular reprogramming is accompanied by a metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Previous results from our laboratory showed that hypoxia alone is able to reprogram primordial germ cells (PGCs) into pluripotency and that this action is mediated by hypoxia-inducible factor 1 (HIF1). As HIF1 exerts a myriad of actions by upregulating several hundred genes, to ascertain whether the metabolic switch toward glycolysis is solely responsible for reprogramming, PGCs were cultured in the presence of a pyruvate kinase M2 isoform (PKM2) activator, or glycolysis was promoted by manipulating PPARγ...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28754874/pyruvate-kinase-m2-deregulation-enhances-the-metastatic-potential-of-tongue-squamous-cell-carcinoma
#6
Wei Wang, Qianting He, Jingjing Sun, Zhonghua Liu, Luodan Zhao, Zhiyuan Lu, Xiaofeng Zhou, Anxun Wang
Pyruvate kinase M2 (PKM2) has been verified to correlate with the prognosis of many types of cancer. However, its role in the development and metastasis of tongue squamous cell carcinoma (TSCC) remains unclear. The immunohistochemistry (IHC) results confirmed that PKM2 is overexpressed in patients with TSCC. PKM2 up-regulation was related to lymph node metastasis and associated with reduced overall survival. According to the microarray analysis and Western blots, PKM2 expression was up-regulated in TSCC cells with enhanced metastatic potential...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753677/pyruvate-kinase-m2-is-a-poor-prognostic-marker-of-and-a-therapeutic-target-in-ovarian-cancer
#7
Tai-Kuang Chao, Tien-Shuo Huang, Yu-Ping Liao, Rui-Lan Huang, Po-Hsuan Su, Hueng-Yuan Shen, Hung-Cheng Lai, Yu-Chi Wang
Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001) and pathogenesis models (p < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28746922/effects-of-pkm2-gene-silencing-on-the-proliferation-and-apoptosis-of-colorectal-cancer-ls-147t-and-sw620-cells
#8
Ran Ao, Lin Guan, Ying Wang, Jia-Ni Wang
BACKGROUND/AIMS: This paper aims to explore the effects of pyruvate kinase (PK) M2 gene silencing on the proliferation and apoptosis of colorectal cancer (CRC) LS-147T and SW620 cells. METHODS: CRC LS-147T and SW620 cells highly expressing PKM2 were randomly selected by quantitative real-time polymerase chain reaction (qRT-PCR) and then assigned into the blank (no transfection), PKM2-shRNA (transfection with shRNA) and empty plasmid (transfection with empty plasmid) groups...
July 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28743549/pyruvate-kinase-m1-interacts-with-a-raf-and-inhibits-endoplasmic-reticulum-stress-induced-apoptosis-by-activating-mek1-erk-pathway-in-mouse-insulinoma-cells
#9
Yuta Horiuchi, Daiki Nakatsu, Fumi Kano, Masayuki Murata
Apoptotic death of pancreatic β cells is a major cause of type 2 diabetes mellitus (T2D) progression. Two isoforms of pyruvate kinase, PKM1 and PKM2, have been reported to participate in cell death in several cell types; however, little is known about their causal pathways in pancreatic β-cell death. We examined whether the suppression of PKM1 or PKM2 affects endoplasmic reticulum (ER) stress-induced apoptosis in a pancreatic β-cell line, MIN6, and Beta-TC-6 and found that knockdown of PKM1, but not of PKM2, leads to the induction of ER stress-induced apoptosis in these cells...
July 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28728385/effects-of-dietary-energy-sources-on-early-postmortem-muscle-metabolism-of-finishing-pigs
#10
Yanjiao Li, Changning Yu, Jiaolong Li, Lin Zhang, Feng Gao, Guanghong Zhou
Objective: This study investigated the effects of different dietary energy sources on early postmortem muscle metabolism of finishing pigs. Methods: Seventy-two barrow (Duroc × Landrace × Yorkshire, DLY) pigs (65.0 ± 2.0 kg) were allotted to three iso-energetic and iso-nitrogenous diets: A (44.1% starch, 5.9% crude fat and 12.6% neutral detergent fibre (NDF)), B (37.6% starch, 9.5% crude fat and 15.4% NDF) or C (30.9% starch, 14.3% crude fat and 17.8% NDF). After the duration of 28-day feeding experiment, 24 pigs (eight per treatment) were slaughtered and the M...
June 26, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28726775/oroxylin-a-activates-pkm1-hnf4-alpha-to-induce-hepatoma-differentiation-and-block-cancer-progression
#11
Libin Wei, Yuanyuan Dai, Yuxin Zhou, Zihao He, Jingyue Yao, Li Zhao, Qinglong Guo, Lin Yang
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28723644/fir-haplodeficiency-promotes-splicing-to-pyruvate-kinase-m2-in-mice-thymic-lymphoma-tissues-revealed-by-six-plex-tandem-mass-tag-quantitative-proteomic-analysis
#12
Asako Kimura, Kouichi Kitamura, Guzhanuer Ailiken, Mamoru Satoh, Toshinari Minamoto, Nobuko Tanaka, Fumio Nomura, Kazuyuki Matsushita
The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28715126/an-engineered-photoswitchable-mammalian-pyruvate-kinase
#13
Stefanie Gehrig, Jamie A Macpherson, Paul C Driscoll, Alastair Symon, Stephen R Martin, James I MacRae, Jens Kleinjung, Franca Fraternali, Dimitrios Anastasiou
Changes in allosteric regulation of glycolytic enzymes have been linked to metabolic reprogramming involved in cancer. Remarkably, allosteric mechanisms control enzyme function at significantly shorter time-scales compared to the long-term effects of metabolic reprogramming on cell proliferation. It remains unclear if and how the speed and reversibility afforded by rapid allosteric control of metabolic enzymes is important for cell proliferation. Tools that allow specific, dynamic modulation of enzymatic activities in mammalian cells would help address this question...
July 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28709426/xue-fu-zhu-yu-decoction-protects-rats-against-retinal-ischemia-by-downregulation-of-hif-1%C3%AE-and-vegf-via-inhibition-of-rbp2-and-pkm2
#14
Shu-Qiu Tan, Xue Geng, Jorn-Hon Liu, Wynn Hwai-Tzong Pan, Li-Xiang Wang, Hui-Kang Liu, Lei Hu, Hsiao-Ming Chao
BACKGROUND: Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia. METHODS: Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed...
July 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28689265/aerobic-glycolysis-hypothesis-through-wnt-beta-catenin-pathway-in-exudative-age-related-macular-degeneration
#15
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Exudative age-related macular degeneration (AMD) is characterized by molecular mechanisms responsible for the initiation of choroidal neovascularization (CNV). Inflammatory processes are associated with upregulation of the canonical WNT/beta-catenin pathway in exudative AMD. We focus this review on the link between WNT/beta-catenin pathway activation and neovascular progression in exudative AMD through activation of aerobic glycolysis for production of angiogenic factors. Increased WNT/beta-catenin pathway involves hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2)...
August 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28688274/discovery-of-novel-naphthoquinone-derivatives-as-inhibitors-of-the-tumor-cell-specific-m2-isoform-of-pyruvate-kinase
#16
Xianling Ning, Hailong Qi, Ridong Li, Yunqiao Li, Yan Jin, Michael A McNutt, Junyi Liu, Yuxin Yin
Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of the glycolytic pathway which is highly expressed in cancer cells. Cancer cells rely heavily on PKM2 for anabolic and energy requirements, and specific targeting of PKM2 therefore has potential as strategy for cancer therapy. Here, we report the synthesis and biologic evaluation of novel naphthoquinone derivatives as selective small molecule inhibitors of PKM2. Some target compounds, such as compound 3k, displayed more potent PKM2 inhibitory activity than the reported optimal PKM2 inhibitor shikonin...
June 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28641694/-mir-133b-affect-the-proliferation-and-drug-sensitivity-in-a549-lung-cancer-stem-cells-by-targeting-pkm2
#17
Yonghua Mi, Miao He, Beizhong Liu
BACKGROUND: It has been proven that miR-133b could inhibit cancer cell growth, the expression level of miR-133b was significant reduction in lung cancer tissue and serum of patients, and increase the radiation sensitivity of squamous cell carcinoma by targeting PKM2, but the exist mechanisms is not clear. The aim of this study is to explore the effect of miR-133b on proliferation in A549 lung cancer stem cells and drug sensitivity in DDP, and to explore the relationship between miR-133b and PKM2 gene, as well as the effect of cancer stem cells...
June 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28641457/antiglioma-pseurotin-a-from-marine-bacillus-sp-fs8d-regulating-tumour-metabolic-enzymes
#18
Komal Anjum, Hongyun Bi, Weiyun Chai, Xiao-Yuan Lian, Zhizhen Zhang
Pseurotin A was isolated from a culture of marine Bacillus sp. FS8D and showed to be active against the proliferation of four different glioma cells with IC50 values of 0.51-29.3 μM. It has been found that pseurotin A downregulated the expression of tumour glycolytic enzymes pyruvate kinase M2 (PKM2) and lactate dehydrogenase 5 (LDH5) and upregulated the expression of pyruvate dehydrogenase beta (PDHB), adenosine triphosphate synthase beta (ATPB) and cytochrome C (Cyto-C), the important regulators for tricarboxylic acid cycle and oxidative phosphorylation...
June 23, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28630053/glucose-catabolism-in-liver-tumors-induced-by-c-myc-can-be-sustained-by-various-pkm1-pkm2-ratios-and-pyruvate-kinase-activities
#19
Andrés Méndez-Lucas, Xiaolei Li, Junjie Hu, Li Che, Xinhua Song, Jiaoyuan Jia, Jingxiao Wang, Chencheng Xie, Paul C Driscoll, Darjus F Tschaharganeh, Diego F Calvisi, Mariia Yuneva, Xin Chen
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Because of differential regulation of enzymatic activities, PKM2, but not PKM1, has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28627476/deciphering-the-protein-protein-interaction-network-regulating-hepatocellular-carcinoma-metastasis
#20
Guoxuan Qin, Mengjiao Dang, Huajun Gao, Hao Wang, Fengting Luo, Ruibing Chen
Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. To better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by quantitative proteomics and bioinformatics analysis. As a result, we identified 378 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that the metabolism and cytoskeleton biological processes are greatly involved with HCC metastasis...
June 14, 2017: Biochimica et Biophysica Acta
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