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https://www.readbyqxmd.com/read/28346425/chip-stub1-regulates-the-warburg-effect-by-promoting-degradation-of-pkm2-in-ovarian-carcinoma
#1
Y Shang, J He, Y Wang, Q Feng, Y Zhang, J Guo, J Li, S Li, Y Wang, G Yan, F Ren, Y Shi, J Xu, N Zeps, Y Zhai, D He, Z Chang
Tumor cells preferentially adopt aerobic glycolysis for their energy supply, a phenomenon known as the Warburg effect. It remains a matter of debate as to how the Warburg effect is regulated during tumor progression. Here, we show that CHIP (carboxyl terminus of Hsc70-interacting protein), a U-box E3 ligase, suppresses tumor progression in ovarian carcinomas by inhibiting aerobic glycolysis. While CHIP is downregulated in ovarian carcinoma, induced expression of CHIP results in significant inhibition of the tumor growth examined by in vitro and in vivo experiments...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28337374/polypyrimidine-tract-binding-protein-1-promotes-proliferation-migration-and-invasion-in-clear-cell-renal-cell-carcinoma-by-regulating-alternative-splicing-of-pkm
#2
Junyi Jiang, Xu Chen, Hao Liu, Jing Shao, Ruihui Xie, Peng Gu, Chaohui Duan
Polypyrimidine Tract-Binding Protein 1 (PTBP1) is an essential RNA-binding protein that regulates diverse biological events through regulating alternative splice of mRNA. PTBP1 induces cancer-promoting splice variants and is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of PTBP1 in clear-cell renal cell carcinoma (ccRCC) are unclear. We investigated PTBP1 expression in 533 ccRCC patients from TCGA and 30 ccRCC patients by immunohistochemistry, and found that PTBP1 expression levels were significantly increased in ccRCC tissues and that high PTBP1 expression was closely correlated with advanced tumor stage, AJCC stage and poor prognosis...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28319058/cytosolic-pkm2-stabilizes-mutant-egfr-protein-expression-through-regulating-hsp90-egfr-association
#3
Y-C Yang, T-Y Cheng, S-M Huang, C-Y Su, P-W Yang, J-M Lee, C-K Chen, M Hsiao, K-T Hua, M-L Kuo
No abstract text is available yet for this article.
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28295642/residual-pyruvate-kinase-activity-in-pklr-deficient-erythroid-precursors-of-a-patient-suffering-from-severe-haemolytic-anaemia
#4
Thomas R L Klei, Sima Kheradmand Kia, Martijn Veldthuis, Boukje M Beuger, Judy Geissler, Javad Dehbozorgian, Mehran Karimi, Robin van Bruggen, Rob van Zwieten
OBJECTIVE: Here we present a 7 year old patient suffering from severe haemolytic anaemia. The most common cause of chronic hereditary non-spherocytic haemolytic anaemia is red blood cell pyruvate kinase (PK-R) deficiency. Since red blood cells rely solely on glycolysis to generate ATP, PK-R deficiency can severely impact energy supply and cause reduction of red blood cell lifespan. We determined the underlying cause of the anaemia and investigated why erythroid precursors in the patient survive...
March 10, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28284859/molecular-mechanisms-of-3-3-4-4-5-pentachlorobiphenyl-induced-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma-cells
#5
Li Song, Linlin Guo, Zhuoyu Li
Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration...
March 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28281967/inhibition-of-proliferation-migration-and-invasion-by-knockdown-of-pyruvate-kinase-m2-pkm2-in-ovarian-cancer-skov3-and-ovcar3-cells
#6
Yi Miao, Meng Lu, Qin Yan, Shuangdi Li, Youji Feng
Pyruvate kinase (PK) is a key enzyme in the process of glycolysis, catalyzing phosphoenolpyruvate (PEP) into pyruvate. Currently, PK isozyme type M2 (PKM2), one subtype of PK, has been proposed as a new tumor marker with high expression in various tumor tissues. Here we aimed to explore the effects of siRNA-PKM2 on ovarian carcinoma (OC) cell lines SKOV3 and OVCAR3, in which PKM2 was notably expressed. PKM2 gene interference lentivirus vectors were built by miRNA transfection assay. siRNA-PKM2-transfected SKOV3 and OVCAR3 cells were evaluated for cell proliferation, cell cycle distribution, cell apoptosis, cell migration, and invasion in this study...
October 27, 2016: Oncology Research
https://www.readbyqxmd.com/read/28259998/enhanced-expression-of-pkm2-associates-with-the-biological-properties-of-cancer-stem-cells-from-a549-human-lung-cancer-cells
#7
Chang-Ying Guo, Chen Yan, Lan Luo, Shinji Goto, Yoshishige Urata, Jian-Jun Xu, Xiao-Ming Wen, Yu-Kang Kuang, Fang-Fang Tou, Tao-Sheng Li
Cancer cells express the M2 isoform of glycolytic enzyme pyruvate kinase (PKM2) for favoring the survival under a hypoxic condition. Considering the relative low oxygen microenvironment in stem cell niche, we hypothesized that an enhanced PKM2 expression associates with the biological properties of cancer stem cells. We used A549 human lung cancer cell line and surgical resected lung cancer tissue samples from patients for experiments. We confirmed the co-localization of PKM2 and CD44, a popular marker for cancer stem cells in lung cancer tissue samples from patients...
February 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28236227/development-of-18-f-dasa-23-for-imaging-tumor-glycolysis-through-noninvasive-measurement-of-pyruvate-kinase-m2
#8
Corinne Beinat, Israt S Alam, Michelle L James, Ananth Srinivasan, Sanjiv Sam Gambhir
PURPOSE: A hallmark of cancer is metabolic reprogramming, which is exploited by cancer cells to ensure rapid growth and survival. Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key step in tumor metabolism and growth. Recently, we reported the radiosynthesis of the first positron emission tomography tracer for visualizing PKM2 in vivo-i.e., [(11)C]DASA-23. Due to the highly promising imaging results obtained with [(11)C]DASA-23 in rodent model glioblastoma, we set out to generate an F-18-labeled version of this tracer, with the end goal of clinical translation in mind...
February 24, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28228400/inhibiting-aerobic-glycolysis-suppresses-renal-interstitial-fibroblasts-activation-and-renal-fibrosis
#9
Hao Ding, Lei Jiang, Jing Xu, Feng Bai, Yang Zhou, Qi Yuan, Jing Luo, Ke Zen, Junwei Yang
Chronic kidney diseases (CKD) generally lead to renal fibrosis. Despite great progresses have been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear and so far no effective therapeutic anti-fibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis, and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28225071/resolution-of-tlr2-induced-inflammation-through-manipulation-of-metabolic-pathways-in-rheumatoid-arthritis
#10
Trudy McGarry, Monika Biniecka, Wei Gao, Deborah Cluxton, Mary Canavan, Siobhan Wade, Sarah Wade, Lorna Gallagher, Carl Orr, Douglas J Veale, Ursula Fearon
During inflammation, immune cells activated by toll-like receptors (TLRs) have the ability to undergo a bioenergetic switch towards glycolysis in a manner similar to that observed in tumour cells. While TLRs have been implicated in the pathogenesis of rheumatoid arthritis (RA), their role in regulating cellular metabolism in synovial cells, however, is still unknown. In this study, we investigated the effect of TLR2-activation on mitochondrial function and bioenergetics in primary RA-synovial fibroblast cells (RASFC), and further determined the role of glycolytic blockade on TLR2-induced inflammation in RASFC using glycolytic inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO)...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213701/ursolic-acid-mediated-changes-in-glycolytic-pathway-promote-cytotoxic-autophagy-and-apoptosis-in-phenotypically-different-breast-cancer-cells
#11
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)). UA-mediated response was more potent than BA-mediated response...
February 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28203090/exploring-targeted-therapy-of-osteosarcoma-using-proteomics-data
#12
Parunya Chaiyawat, Jongkolnee Settakorn, Apiruk Sangsin, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Aungsumalee Soongkhaw, Dumnoensun Pruksakorn
Despite multimodal therapeutic treatments of osteosarcoma (OS), some patients develop resistance to currently available regimens and eventually end up with recurrent or metastatic outcomes. Many attempts have been made to discover effective drugs for improving outcome; however, due to the heterogeneity of the disease, new therapeutic options have not yet been identified. This study aims to explore potential targeted therapy related to protein profiles of OS. In this review of proteomics studies, we extracted data on differentially expressed proteins (DEPs) from archived literature in PubMed and our in-house repository...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28183315/pyruvate-kinase-m2-and-the-mitochondrial-atpase-inhibitory-factor-1-provide-novel-biomarkers-of-dermatomyositis-a-metabolic-link-to-oncogenesis
#13
Fulvio Santacatterina, María Sánchez-Aragó, Marc Catalán-García, Glòria Garrabou, Cristina Nuñez de Arenas, Josep M Grau, Francesc Cardellach, José M Cuezva
BACKGROUND: Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. METHODS: A cohort of thirty-two muscle biopsies and forty plasma samples comprising polymyositis (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) and control donors was interrogated with monoclonal antibodies against proteins of energy metabolism using reverse phase protein microarrays (RPPA)...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28183280/whole-genome-scan-reveals-the-genetic-signature-of-african-ankole-cattle-breed-and-potential-for-higher-quality-beef
#14
Mengistie Taye, Jaemin Kim, Sook Hee Yoon, Wonseok Lee, Olivier Hanotte, Tadelle Dessie, Stephen Kemp, Okeyo Ally Mwai, Kelsey Caetano-Anolles, Seoae Cho, Sung Jong Oh, Hak-Kyo Lee, Heebal Kim
BACKGROUND: Africa is home to numerous cattle breeds whose diversity has been shaped by subtle combinations of human and natural selection. African Sanga cattle are an intermediate type of cattle resulting from interbreeding between Bos taurus and Bos indicus subspecies. Recently, research has asserted the potential of Sanga breeds for commercial beef production with better meat quality as compared to Bos indicus breeds. Here, we identified meat quality related gene regions that are positively selected in Ankole (Sanga) cattle breeds as compared to indicus (Boran, Ogaden, and Kenana) breeds using cross-population (XP-EHH and XP-CLR) statistical methods...
February 9, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28122247/arginine-deprivation-inhibits-the-warburg-effect-and-upregulates-glutamine-anaplerosis-and-serine-biosynthesis-in-ass1-deficient-cancers
#15
Jeff Charles Kremer, Bethany Cheree Prudner, Sara Elaine Stubbs Lange, Gregory Richard Bean, Matthew Bailey Schultze, Caitlyn Brook Brashears, Megan DeAnna Radyk, Nathan Redlich, Shin-Cheng Tzeng, Kenjiro Kami, Laura Shelton, Aixiao Li, Zack Morgan, John Stephen Bomalaski, Takashi Tsukamoto, Jon McConathy, Loren Scott Michel, Jason Matthew Held, Brian Andrew Van Tine
Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28092997/the-t-8-21-fusion-protein-runx1-eto-downregulates-pkm2-in-acute-myeloid-leukemia-cells
#16
Jin-Song Yan, Yi-Dong Li, Su-Hui Liu, Qian-Qian Yin, Xin-Yi Liu, Li Xia, Ying Lu
No abstract text is available yet for this article.
August 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#17
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
#18
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
#19
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
#20
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
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