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https://www.readbyqxmd.com/read/28454440/ffj-3-inhibits-pkm2-protein-expression-via-the-pi3k-akt-signaling-pathway-and-activates-the-mitochondrial-apoptosis-signaling-pathway-in-human-cancer-cells
#1
Dengyun Li, Xiaoli Wei, Mingming Ma, Huina Jia, Yu Zhang, Wenyi Kang, Tianxiao Wang, Xiaoyan Shi
Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and potential therapeutic target for the treatment of cancer. In the present study, FFJ-3, a structurally modified version of mollugin, an extract of the Traditional Chinese herbal medicine Rubia tinctorum (madder) was used in order to determine the anticancer activity of the compound and investigate the potential mechanisms underlying this effect in human cancer cells. The results of the present study revealed that FFJ-3 inhibited the survival of HepG2 human hepatoma cells, MCF-7 human breast cancer cells and A549 human lung adenocarcinoma cells using the MTT assay...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28446743/mammalian-target-of-rapamycin-mtor-regulates-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-via-decreased-pyruvate-kinase-m2-pkm2-expression-in-cervical-cancer-cells
#2
Ke-Yan Cheng, Min Hao
BACKGROUND Epithelial-mesenchymal transition (EMT) plays an important role in cancer tumorigenesis. Transforming growth factor β1 (TGF-β1) can induced EMT, which could increase tumor migration and invasion. Moreover, recent studies have been proven that mammalian target of rapamycin (mTOR) is a critical regulator of EMT. We investigated the mechanisms of mTOR in transforming growth factor β1 (TGF-β1)-induced EMT in cervical cancer cells. MATERIAL AND METHODS HeLa and SiHa cells were treated with 10 ng/ml TGF-β1 to induce EMT...
April 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#3
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28426732/regulation-of-sesame-mediated-h3t11-phosphorylation-by-glycolytic-enzymes-and-metabolites
#4
Qi Yu, Chong Tong, Mingdan Luo, Xiangyan Xue, Qianyun Mei, Lixin Ma, Xiaolan Yu, Wuxiang Mao, Lingbao Kong, Xilan Yu, Shanshan Li
Cancer cells prefer aerobic glycolysis, but little is known about the underlying mechanism. Recent studies showed that the rate-limiting glycolytic enzymes, pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to regulate gene expression and cell proliferation, revealing its non-metabolic functions in connecting glycolysis and histone modifications. We have reported that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene expression and oxidative stress resistance. But how glycolysis regulates H3T11 phosphorylation remains unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28423551/metabolic-reprogramming-of-the-premalignant-colonic-mucosa-is-an-early-event-in-carcinogenesis
#5
Mart Dela Cruz, Sarah Ledbetter, Sanjib Chowdhury, Ashish K Tiwari, Navneet Momi, Ramesh K Wali, Charles Bliss, Christopher Huang, David Lichtenstein, Swati Bhattacharya, Anisha Varma-Wilson, Vadim Backman, Hemant K Roy
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422979/correlation-of-egfr-or-kras-mutation-status-with-18f-fdg-uptake-on-pet-ct-scan-in-lung-adenocarcinoma
#6
Kazuya Takamochi, Kaoru Mogushi, Hideya Kawaji, Kota Imashimizu, Mariko Fukui, Shiaki Oh, Masayoshi Itoh, Yoshihide Hayashizaki, Weijey Ko, Masao Akeboshi, Kenji Suzuki
BACKGROUND: 18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on glucose metabolism. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV) of 18F-FDG PET scanning has not been fully elucidated. METHODS: Correlations between EGFR or KRAS mutation status and clinicopathological factors including SUVmax were statistically analyzed in 734 surgically resected lung adenocarcinoma patients...
2017: PloS One
https://www.readbyqxmd.com/read/28418088/rack1-forms-a-complex-with-fgfr1-and-pkm2-and-stimulates-the-growth-and-migration-of-squamous-lung-cancer-cells
#7
Chengzhi Zhou, Tao Chen, Zhanhong Xie, Yinyin Qin, Yangming Ou, Jiexia Zhang, Shiyue Li, Rongchang Chen, Nanshan Zhong
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer. Better understanding the regulation of this process would benefit the clinical treatment for lung cancer. Here, it has been found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and inhibited the growth and migration of lung cancer cells, while over-expression of RACK1 in lung cancer cells led to the resistance to Erdafitinib...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28415668/mir-let-7a-inhibits-cell-proliferation-migration-and-invasion-by-down-regulating-pkm2-in-cervical-cancer
#8
Man Guo, Xinying Zhao, Xiaolei Yuan, Jing Jiang, Peiling Li
In recent decades, miRNA has been reported as a crucial modulator in some biology progressions. This work aims to assess the expression and role of miR-let-7a and pyruvate kinase muscle isozyme M2 (PKM2) in CC tissues and cell lines. Here, we identified that miR-let-7a expression was decreased in CC tissues, and SiHa and HeLa cells (all P < 0.001), however, PKM2 expression was increased in these samples. Statistically, miR-let-7a was inversely associated with PKM2 mRNA or protein (p = 0.013, p = 0.015, respectively)...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414323/pyrimidine-tract-binding-protein-1-mediates-pyruvate-kinase-m2-dependent-phosphorylation-of-signal-transducer-and-activator-of-transcription-3-and-oncogenesis-in-anaplastic-large-cell-lymphoma
#9
Steven R Hwang, Carlos Murga-Zamalloa, Noah Brown, Johnvesly Basappa, Scott Rp McDonnell, Veronica Mendoza-Reinoso, Venkatesha Basrur, Ryan Wilcox, Kojo Elenitoba-Johnson, Megan S Lim
PKM2 (pyruvate kinase M2), a critical regulator of glycolysis, is phosphorylated by numerous growth factor receptors and oncogenic tyrosine kinases including NPM-ALK which is expressed in a subset of aggressive T-cell non-Hodgkin lymphomas known as anaplastic large cell lymphoma, ALK-positive. Our previous work demonstrated that phosphorylation of Y105-PKM2 by NPM-ALK regulates a major metabolic shift to promote lymphomagenesis. In addition to its role in metabolism, recent studies have shown that PKM2 promotes oncogenesis by phosphorylating nuclear STAT3 (signal transducer and activator of transcription 3) and regulating transcription of genes involved in cell survival and proliferation...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28398453/multi-step-encapsulation-of-chemotherapy-and-gene-silencing-agents-in-functionalized-mesoporous-silica-nanoparticles
#10
Jianliang Shen, Haoran Liu, Chaofeng Mu, Joy Wolfram, Wei Zhang, Han-Cheon Kim, Guixian Zhu, Zhongbo Hu, Liang-Nian Ji, Xuewu Liu, Mauro Ferrari, Zong-Wan Mao, Haifa Shen
Drug to carrier ratio is an important consideration in designing drug platforms, since a low loading capacity necessitates the use of high doses of carriers, which can result in side effects. Here, we have engineered a platform to co-deliver small molecule drugs and small interfering RNA (siRNA). This platform consists of cyclodextrin-grafted polyethylenimine (CP) functionalized mesoporous silica nanoparticles (MSNP). A unique multi-step encapsulation procedure was used to obtain a high loading capacity for doxorubicin (DOX) and siRNA oligos specific for the PKM2 gene that encodes pyruvate kinase M2, an enzyme catalyzing the final rate-limiting step in glycolysis...
April 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28394882/mir-4417-targets-tripartite-motif-containing-35-trim35-and-regulates-pyruvate-kinase-muscle-2-pkm2-phosphorylation-to-promote-proliferation-and-suppress-apoptosis-in-hepatocellular-carcinoma-cells
#11
Lijie Song, Weijie Zhang, Zhiwei Chang, Yanfeng Pan, Hong Zong, Qingxia Fan, Liuxing Wang
BACKGROUND MicroRNAs (miRNAs) are a class of small non-coding RNAs that are strongly involved in various types of carcinogenesis, including hepatocellular carcinoma (HCC). This study aimed to clarify whether miR-4417 promotes HCC growth by targeting TRIM35 and regulating PKM2 phosphorylation. MATERIAL AND METHODS Online software, including TargetScan and miRanda, was used to predict the potential target of miR-4417. Real-Time PCR (qRT-PCR) and Western blot assays were performed to detect the expression levels of mRNA and protein, respectively...
April 10, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28393220/metformin-increases-sensitivity-of-osteosarcoma-stem-cells-to-cisplatin-by-inhibiting-expression-of-pkm2
#12
Depeng Shang, Ju Wu, Lianyi Guo, Yanju Xu, Lezi Liu, Jianmin Lu
Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared cisplatin sensitivity between OS stem cells and OS non-stem cells. We confirmed that OS stem cells showed significant cisplatin-resistance compared with the OS non-CSCs. Mechanically, we proved that overexpression of the pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to cisplatin in OS stem cells...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28380434/inos-derived-nitric-oxide-promotes-glycolysis-by-inducing-pyruvate-kinase-m2-nuclear-translocation-in-ovarian-cancer
#13
Linlin Li, Lingqun Zhu, Bingtao Hao, Wenwen Gao, Qianli Wang, Keyi Li, Meng Wang, Mengqiu Huang, Zhengjun Liu, Qiaohong Yang, Xiqing Li, Zhuo Zhong, Wenhua Huang, Guanghui Xiao, Yang Xu, Kaitai Yao, Qiuzhen Liu
Aerobic glycolysis is essential for tumor growth and survival. Activation of multiple carcinogenic signals contributes to metabolism reprogramming during malignant transformation of cancer. Recently nitric oxide has been noted to promote glycolysis but the mechanism remains elusive. We report here the dual role of nitric oxide in glycolysis: low/physiological nitric oxide (≤ 100 nM) promotes glycolysis for ATP production, oxidative defense and cell proliferation of ovary cancer cells, whereas excess nitric oxide (≥ 500 nM) inhibits it...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28378811/inhibition-of-pyruvate-kinase-m2-markedly-reduces-chemoresistance-of-advanced-bladder-cancer-to-cisplatin
#14
Xing Wang, Fenglin Zhang, Xue-Ru Wu
Chemoresistance to cisplatin is a principal cause of treatment failure and mortality of advanced bladder cancer (BC). The underlying mechanisms remain unclear, which hinders the development of preventive strategies. Recent data indicate that pyruvate kinase M2 (PKM2), a glycolytic enzyme for Warburg effect, is strongly upregulated in BC. This study explores the role of PKM2 in chemoresistance and whether inhibiting PKM2 augments the chemosensitivity to cisplatin and reduces BC growth and progression. We found that Shikonin binds PKM2 and inhibits BC cell survival in a dose-dependent but pyruvate kinase activity-independent manner...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28356960/induction-of-apoptosis-by-ffj-5-a-novel-naphthoquinone-compound-occurs-via-downregulation-of-pkm2-in-a549-and-hepg2-cells
#15
Xiaoli Wei, Ming Li, Mingming Ma, Huina Jia, Yu Zhang, Wenyi Kang, Tianxiao Wang, Xiaoyan Shi
Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and as a potential target for cancer therapy. In this study, F§FJ-5, a characterized naphthoquinone modifier of mollugin, was synthesized in order to investigate its anticancer activity and the potential mechanisms. It was observed that FFJ-5 inhibited the cell growth of human lung adenocarcinoma cells A549 and human hepatoma cells HepG2 by MTT assays. FFJ-5 arrested cell cycle at the G2/M phase. Further analyses demonstrated that FFJ-5 attenuated the expression of PKM2 and reduced the production of adenosine triphosphate (ATP)...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28346425/chip-stub1-regulates-the-warburg-effect-by-promoting-degradation-of-pkm2-in-ovarian-carcinoma
#16
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
#17
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
#18
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
#19
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
#20
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...
May 1, 2017: Toxicology and Applied Pharmacology
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