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PKM2

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https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#1
Zhimin Gu, Jiliang Xia, Hongwei Xu, Ivana Frech, Guido Tricot, Fenghuang Zhan
BACKGROUND: Aerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival. METHODS: Tandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28067230/pyruvate-kinase-type-m2-promotes-tumour-cell-exosome-release-via-phosphorylating-synaptosome-associated-protein-23
#2
Yao Wei, Dong Wang, Fangfang Jin, Zhen Bian, Limin Li, Hongwei Liang, Mingzhen Li, Lei Shi, Chaoyun Pan, Dihan Zhu, Xi Chen, Gang Hu, Yuan Liu, Chen-Yu Zhang, Ke Zen
Tumour cells secrete exosomes that are involved in the remodelling of the tumour-stromal environment and promoting malignancy. The mechanisms governing tumour exosome release, however, remain incompletely understood. Here we show that tumour cell exosomes secretion is controlled by pyruvate kinase type M2 (PKM2), which is upregulated and phosphorylated in tumours. During exosome secretion, phosphorylated PKM2 serves as a protein kinase to phosphorylate synaptosome-associated protein 23 (SNAP-23), which in turn enables the formation of the SNARE complex to allow exosomes release...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28060337/using-rna-sequencing-to-detect-novel-splice-variants-related-to-drug-resistance-in-in-vitro-cancer-models
#3
Rocco Sciarrillo, Anna Wojtuszkiewicz, Irsan E Kooi, Valentina E Gómez, Ugo Boggi, Gerrit Jansen, Gert-Jan Kaspers, Jacqueline Cloos, Elisa Giovannetti
Drug resistance remains a major problem in the treatment of cancer for both hematological malignancies and solid tumors. Intrinsic or acquired resistance can be caused by a range of mechanisms, including increased drug elimination, decreased drug uptake, drug inactivation and alterations of drug targets. Recent data showed that other than by well-known genetic (mutation, amplification) and epigenetic (DNA hypermethylation, histone post-translational modification) modifications, drug resistance mechanisms might also be regulated by splicing aberrations...
December 9, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28049773/crosstalk-between-alternatively-spliced-ugt1a-isoforms-and-colon-cancer-cell-metabolism
#4
Yannick Audet-Delage, Michele Rouleau, Melanie Rouleau, Joannie Roberge, Stephanie Miard, Frederic Picard, Bernard Tetu, Chantal Guillemette
Alternative splicing at the human glucuronosyltransferase 1 gene locus (UGT1) produces alternate isoforms UGT1A_i2s that control glucuronidation activity through protein-protein interactions. Here, we hypothesized that UGT1A_i2s function into a complex protein network connecting other metabolic pathways with influence on cancer cell metabolism. This is based on a pathway enrichment analysis of proteomic data that identified several high-confidence candidate interaction proteins of UGT1A_i2 proteins in human tissues, namely the rate-limiting enzyme of glycolysis pyruvate kinase (PKM), which plays a critical role in cancer cell metabolism and tumor growth...
January 3, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28049552/antiproliferative-cyclodepsipeptides-from-the-marine-actinomycete-streptomyces-sp-p11-23b-downregulating-the-tumor-metabolic-enzymes-of-glycolysis-glutaminolysis-and-lipogenesis
#5
Xuewei Ye, Komal Anjum, Tengfei Song, Wenling Wang, Ying Liang, Mengxuan Chen, Haocai Huang, Xiao-Yuan Lian, Zhizhen Zhang
Two cyclodepsipeptides and a known cyclodepsipeptide valinomycin were isolated from a culture of the marine actinomycete Streptomyces sp. P11-23B. Their structures were established based on NMR, HRESIMS, and MS-MS spectroscopic interpretation as well as by chemical degradation. Both streptodepsipeptides P11A and P11B inhibited proliferation of different glioma cell lines, with IC50 values ranging from 0.1 μM to 1.4 μM. Streptodepsipeptide P11A was found to block the cell cycle at the G0/G1 phase and induce apoptosis in glioma cells...
December 31, 2016: Phytochemistry
https://www.readbyqxmd.com/read/28036303/desuccinylation-of-pyruvate-kinase-m2-by-sirt5-contributes-to-antioxidant-response-and-tumor-growth
#6
Ye Xiangyun, Niu Xiaomin, Gu Linping, Xu Yunhua, Li Ziming, Yu Yongfeng, Chen Zhiwei, Lu Shun
Tumor cells trends to express high level of pyruvate kinase M2 (PKM2). The inhibition of PKM2 activity is needed for antioxidant response by diverting glucose flux into the pentose phosphate pathway and thus generating sufficient reducing potential. Here we report that PKM2 is succinylated at lysine 498 (K498) and succinylation increases its activity. SIRT5 binds to, desuccinylates and inhibits PKM2 activity. Increased level of reactive oxygen species (ROS) decreases both the succinylation and activity of PKM2 by increasing its binding to SIRT5...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035139/mitochondrial-pkm2-regulates-oxidative-stress-induced-apoptosis-by-stabilizing-bcl2
#7
Ji Liang, Ruixiu Cao, Xiongjun Wang, Yajuan Zhang, Pan Wang, Hong Gao, Chen Li, Fan Yang, Rong Zeng, Ping Wei, Dawei Li, Wenfeng Li, Weiwei Yang
Pyruvate kinase M2 isoform (PKM2) catalyzes the last step of glycolysis and plays an important role in tumor cell proliferation. Recent studies have reported that PKM2 also regulates apoptosis. However, the mechanisms underlying such a role of PKM2 remain elusive. Here we show that PKM2 translocates to mitochondria under oxidative stress. In the mitochondria, PKM2 interacts with and phosphorylates Bcl2 at threonine (T) 69. This phosphorylation prevents the binding of Cul3-based E3 ligase to Bcl2 and subsequent degradation of Bcl2...
December 30, 2016: Cell Research
https://www.readbyqxmd.com/read/28025580/pkm2-and-other-key-regulators-of-warburg-effect-positively-correlate-with-cd147-emmprin-gene-expression-and-predict-survival-in-multiple-myeloma
#8
S Panchabhai, I Schlam, S Sebastian, R Fonseca
Leukemia accepted article preview online, 27 December 2016. doi:10.1038/leu.2016.389.
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27989750/the-antioxidant-uncoupling-protein-2-stimulates-hnrnpa2-b1-glut1-and-pkm2-expression-and-sensitizes-pancreas-cancer-cells-to-glycolysis-inhibition
#9
Jessica Brandi, Daniela Cecconi, Marco Cordani, Margalida Torrens-Mas, Raffaella Pacchiana, Elisa Dalla Pozza, Giovanna Butera, Marcello Manfredi, Emilio Marengo, Jordi Oliver, Pilar Roca, Ilaria Dando, Massimo Donadelli
Several evidence indicate that metabolic alterations play a pivotal role in cancer development. Here, we report that the mitochondrial uncoupling protein 2 (UCP2) sustains the metabolic shift from mitochondrial oxidative phosphorylation (mtOXPHOS) to glycolysis in pancreas cancer cells. Indeed, we show that UCP2 sensitizes pancreas cancer cells to the treatment with the glycolytic inhibitor 2-deoxy-D-glucose. Through a bidimensional electrophoresis analysis, we identify 19 protein species differentially expressed after treatment with the UCP2 inhibitor genipin and, by bioinformatic analyses, we show that these proteins are mainly involved in metabolic processes...
October 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27978618/electrophilic-modification-of-pkm2-by-4-hydroxynonenal-and-4-oxononenal-results-in-protein-cross-linking-and-kinase-inhibition
#10
Jeannie M Camarillo, Jody C Ullery, Kristie L Rose, Lawrence J Marnett
Rapidly proliferating cells require an increased rate of metabolism to allow for the production of nucleic acids, amino acids, and lipids. Pyruvate kinase catalyzes the final step in the glycolysis pathway, and different isoforms display vastly different catalytic efficiencies. The M2 isoform of pyruvate kinase (PKM2) is strongly expressed in cancer cells and contributes to aerobic glycolysis in what is commonly termed the Warburg effect. Here, we show that PKM2 is covalently modified by the lipid electrophiles 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE)...
January 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27960279/resveratrol-induces-cancer-cell-apoptosis-through-mir-326-pkm2-mediated-er-stress-and-mitochondrial-fission
#11
Haili Wu, Yingying Wang, Changxin Wu, Peng Yang, Hanqing Li, Zhuoyu Li
Resveratrol (Res), a natural phytoalexin found in a variety of plants, has significant antitumor activity. Pyruvate kinase M2 (PKM2) has abnormally high expression in various tumor cells, and it has been implicated in the survival of tumors. However, whether and how Res inhibits PKM2 expression is poorly understood. In the present study, we found that treatment with Res inhibited cell proliferation and induced cell apoptosis. The IC50 values of Res against DLD1, HeLa, and MCF-7 cells were 75 ± 4.54, 50 ± 3...
December 14, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27916907/metformin-inhibits-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-via-pkm2-relative-mtor-p70s6k-signaling-pathway-in-cervical-carcinoma-cells
#12
Keyan Cheng, Min Hao
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) plays a prominent role in tumorigenesis. Metformin exerts antitumorigenic effects in various cancers. This study investigated the mechanisms of metformin in TGF-β1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells. METHODS: cells were cultured with 10 ng/mL TGF-β1 to induce EMT and treated with or without metformin. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis were analyzed by flow cytometry; cell migration was evaluated by wound-healing assay...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27911861/pyruvate-kinase-m2-pkm2-expression-correlates-with-prognosis-in-solid-cancers-a-meta-analysis
#13
Haiyan Zhu, Hui Luo, Xuejie Zhu, Xiaoli Hu, Lihong Zheng, Xueqiong Zhu
Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27908730/mtor-activation-is-critical-for-betulin-treatment-in-renal-cell-carcinoma-cells
#14
Wenlong Cheng, Shiqi Ji, Haijian Zhang, Zhixing Han, Qingjun Liu, Jianwen Wang, Hao Ping
Betulin, a natural product isolated from the bark of the birch trees, exhibits multiple anticancer effects. Activation of mTOR signaling pathway has been found in numerous cancers, including renal cell carcinoma (RCC). Here, we attempted to study whether mTOR signaling was essential for betulin to treat RCC. Based on cell survival and colony formation assays, we found that mTOR hyperactive RCC cell line 786-O cells were more sensitive to betulin treatment compared with mTOR-inactive Caki-2 cells. Knockdown of TSC2 in Caki-2 cells had similar results to 786-O cells, and mTOR silencing in 786-O cells rescued the inhibitory effect of betulin, indicating that betulin inhibited RCC cell proliferation in an mTOR-dependent manner...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27903739/homocysteine-activates-b-cells-via-regulating-pkm2-dependent-metabolic-reprogramming
#15
Jiacheng Deng, Silin Lü, Huiying Liu, Bo Liu, Changtao Jiang, Qingbo Xu, Juan Feng, Xian Wang
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894667/nuclear-pkm2-expression-an-independent-risk-factor-for-er-after-curative-resection-of-hepatocellular-carcinoma
#16
Fangtian Fan, Hongyan Wu, Zhaoguo Liu, Xianbang Hou, Wenxin Chen, Aiyun Wang, Yin Lu
Surgical resection, providing a long-term survival of hepatocellular carcinoma (HCC) patients, is regarded as one of the standard curative treatments of HCC if the tumor is resectable. However, 50% patients develop early recurrence (ER) during the first two years after operation, which are more diffuse and rarely treatable with unsatisfactory long-term survival. Unfortunately, the underlying mechanisms of ER after curative resection and the molecular markers with predictive and prognostic significance have never been identified yet...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27883057/the-warburg-effect-mediator-pyruvate-kinase-m2-expression-and-regulation-in-the-retina
#17
Raju V S Rajala, Ammaji Rajala, Christopher Kooker, Yuhong Wang, Robert E Anderson
The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose, even in the presence of oxygen. Retinal photoreceptors are highly metabolic and their energy consumption is equivalent to that of a multiplying tumor cell. In the present study, we found that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and that it undergoes a light-dependent tyrosine phosphorylation...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879277/eukaryotic-translation-initiation-factor-5a2-promotes-metabolic-reprogramming-in-hepatocellular-carcinoma-cells
#18
Ting-Ting Cao, Shu-Hai Lin, Li Fu, Zhi Tang, Chi-Ming Che, Li-Yi Zhang, Xiao-Yan Ming, Teng-Fei Liu, Xu-Ming Tang, Bin-Bin Tan, Di Xiang, Feng Li, On-Yee Chan, Dan Xie, Zongwei Cai, Xin-Yuan Guan
Reprogramming of intracellular metabolism is common in liver cancer cells. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. In our previous study, we reported that a novel oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) promotes tumorigenesis under hypoxic condition. Here, we aim to investigate the role of EIF5A2 in cell metabolic reprogramming during hepatocellular carcinoma (HCC) development. In this study, we reported that the messenger RNA (mRNA) level of EIF5A2 was upregulated in 59 of 105 (56...
January 2017: Carcinogenesis
https://www.readbyqxmd.com/read/27875786/inflammation-dysregulated-metabolism-and-aromatase-in-obesity-and-breast-cancer
#19
REVIEW
Heba Zahid, Evan R Simpson, Kristy A Brown
Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#20
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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