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AMPK AND cancer

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https://www.readbyqxmd.com/read/28628081/o-glcnacylation-of-fumarase-maintains-tumour-growth-under-glucose-deficiency
#1
Ting Wang, Qiujing Yu, Jingjie Li, Bin Hu, Qin Zhao, Chunmin Ma, Wenhua Huang, Lingang Zhuo, Houqin Fang, Lujian Liao, Y Eugene Chin, Yuhui Jiang
Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28622524/ampk-mechanisms-of-cellular-energy-sensing-and-restoration-of-metabolic-balance
#2
REVIEW
Daniel Garcia, Reuben J Shaw
AMPK is a highly conserved master regulator of metabolism, which restores energy balance during metabolic stress both at the cellular and physiological levels. The identification of numerous AMPK targets has helped explain how AMPK restores energy homeostasis. Recent advancements illustrate novel mechanisms of AMPK regulation, including changes in subcellular localization and phosphorylation by non-canonical upstream kinases. Notably, the therapeutic potential of AMPK is widely recognized and heavily pursued for treatment of metabolic diseases such as diabetes, but also obesity, inflammation, and cancer...
June 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#3
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618116/differences-in-p53-status-significantly-influence-the-cellular-response-and-cell-survival-to-1-25-dihydroxyvitamin-d3-metformin-cotreatment-in-colorectal-cancer-cells
#4
Mohamed A Abu El Maaty, Wendy Strassburger, Tooba Qaiser, Yasamin Dabiri, Stefan Wölfl
Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC cell lines HCT116 wild-type (wt), HCT116 p53-/- and HT-29 (mutant; R273H) were employed, covering 3 different p53 variations...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28617309/lipid-storage-and-autophagy-in-melanoma-cancer-cells
#5
Claudia Giampietri, Simonetta Petrungaro, Martina Cordella, Claudio Tabolacci, Luana Tomaipitinca, Antonio Facchiano, Adriana Eramo, Antonio Filippini, Francesco Facchiano, Elio Ziparo
Cancer stem cells (CSC) represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1) and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ)...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28616582/a-new-duet-in-cancer-biology-ampk-the-typical-and-ube2o-the-atypical
#6
Isabelle K Vila, Su Jung Song, Min Sup Song
Ubiquitin-conjugating enzyme E2O (UBE2O) is upregulated in human cancers. We have demonstrated that genetic deletion or pharmacological blockade of UBE2O reduces tumorigenesis through inhibiting the mammalian target of rapamycin complex 1-hypoxia-inducible factor 1-α pathway. Critically, UBE2O targets adenosine monophosphate (AMP)-activated protein kinase-α 2 (AMPKα2) for ubiquitination and degradation. We thus suggest the UBE2O-AMPKα2 axis as a potential therapeutic target for cancer.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28615957/erratum-isoorientin-induces-apoptosis-decreases-invasiveness-and-downregulates-vegf-secretion-by-activating-ampk-signaling-in-pancreatic-cancer-cells-corrigendum
#7
(no author information available yet)
[This corrects the article on p. 7481 in vol. 9, PMID: 28003763.].
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28611773/fatty-acid-oxidation-compensates-for-lipopolysaccharide-induced-warburg-effect-in-glucose-deprived-monocytes
#8
Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefan Rubner, Sven Baumann, Martin von Bergen, Antje Körner, Martin Krueger, Manuela Rossol, Ulf Wagner
Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28609310/blockade-of-glut1-by-wzb117-resensitizes-breast-cancer-cells-to-adriamycin
#9
Qing Chen, Ya-Qiu Meng, Xiao-Fan Xu, Jun Gu
The tolerance to adriamycin of cancer as a common and stubborn obstacle occurred during curing breast cancer patients needs to be overcome. In the present study, we explored whether inhibiting the glucose transporter 1 (GLUT1) could restore the activity of adriamycin in breast cancer cell line MCF-7 resistant to adriamycin and the possible underlying mechanisms. Adriamycin-resistant cell line MCF-7/ADR was selected stepwise from the parental MCF-7 cells and the level of GLUT1 was measured. Then, the MCF-7/ADR cells were incubated with adriamycin, WZB117 (a specific GLUT1 inhibitor), or both...
June 12, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28599494/cucurbitacin-e-induces-apoptosis-of-human-prostate-cancer-cells-via-cofilin-1-and-mtorc1
#10
Xiaolong He, Qi Gao, Yayong Qiang, Wei Guo, Yadong Ma
Cucurbitacin E is an important member of the cucurbitacin family and exhibits inhibitory effects in various types of cancer. Cucurbitacin is a potential antineoplastic drug; however, its anticancer effect in human prostate cancer (PC) remains unknown. The aim of the present study was to determine whether the effect of cucurbitacin E on the cell viability and apoptosis of the human PC cell line, LNCaP, was mediated by cofilin-1- and mammalian target of rapamycin (mTOR). The results of the present study demonstrated that cucurbitacin E significantly exhibited cytotoxicity, suppressed cell viability (P<0...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598969/cucurbitacin-e-reduces-obesity-and-related-metabolic-dysfunction-in-mice-by-targeting-jak-stat5-signaling-pathway
#11
Munazza Murtaza, Gulnaz Khan, Meha Fatima Aftab, Shabbir Khan Afridi, Safina Ghaffar, Ayaz Ahmed, Rahman M Hafizur, Rizwana Sanaullah Waraich
Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic syndrome (MetS)...
2017: PloS One
https://www.readbyqxmd.com/read/28596475/enhanced-efficacy-of-akt-and-fak-kinase-combined-inhibition-in-squamous-cell-lung-carcinomas-with-stable-reduction-in-pten
#12
Andrea Cavazzoni, Silvia La Monica, Roberta Alfieri, Andrea Ravelli, Nele Van Der Steen, Rocco Sciarrillo, Denise Madeddu, Costanza Anna Maria Lagrasta, Federico Quaini, Mara Bonelli, Claudia Fumarola, Daniele Cretella, Graziana Digiacomo, Marcello Tiseo, Godefridus J Peters, Andrea Ardizzoni, Pier Giorgio Petronini, Elisa Giovannetti
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591720/brsk2-induced-by-nutrient-deprivation-promotes-akt-activity-in-pancreatic-cancer-via-downregulation-of-mtor-activity
#13
Hexige Saiyin, Ning Na, Xu Han, Yuan Fang, Yanhua Wu, Wenhui Lou, Xianmei Yang
Neoplastic cells in pancreatic ductual adenocarcinoma (PDAC) survive in an energy-deprived milieu, and hyper-activation of Akt is thought to contribute to the neoplastic cell survival in PDAC. Kras activating mutations, common in PDAC, was believed to be the major driver of Akt activation. However, the inhibitor to Kras was not therapeutic for PDAC patients. This implied that PDAC cells might harbor an intrinsic merit that strengthens Akt activity. Here we showed that BRSK2, a serine/threonine-protein kinase of AMPK family, was induced by nutrient deprivation in PDAC cells and suppressed mTORC1 activity via phosphorylation of tuberous sclerosis complex 2 (TSC2)...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28581641/clk1-regulated-aerobic-glycolysis-is-involved-in-gliomas-chemoresistance
#14
Li Zhang, Huicui Yang, Wenbin Zhang, Zhongqin Liang, Qiang Huang, Guoqiang Xu, Xuechu Zhen, Long Tai Zheng
Chemoresistance remains a major challenge for the treatment of glioma. In the present study, we investigated the role of Clk1, which encodes an enzyme that is necessary for ubiquinone biosynthesis in glioma chemoresistance in vitro. The results showed that Clk1 was highly expressed in GL261 mouse glioma cells which were most sensitive to BCNU while was expressed in BCNU resistant cells such as glioma cancer stem cells: T98G, U87MG and U251 glioma cells at low levels. Knockdown of Clk1 in GL261 glioma cells significantly reduced BCNU- or cisplatin- induced cell apoptosis whereas the proliferative activity and the expression of multi-drug resistance -related genes including MDR1, MGMT and GSTP1 were not changed...
June 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28581518/activation-of-tumor-suppressor-lkb1-by-honokiol-abrogates-cancer-stem-like-phenotype-in-breast-cancer-via-inhibition-of-oncogenic-stat3
#15
S Sengupta, A Nagalingam, N Muniraj, M Y Bonner, P Mistriotis, A Afthinos, P Kuppusamy, D Lanoue, S Cho, P Korangath, M Shriver, A Begum, V F Merino, C-Y Huang, J L Arbiser, W Matsui, B Győrffy, K Konstantopoulos, S Sukumar, P A Marignani, N K Saxena, D Sharma
Tumor suppressor and upstream master kinase Liver kinase B1 (LKB1) plays a significant role in suppressing cancer growth and metastatic progression. We show that low-LKB1 expression significantly correlates with poor survival outcome in breast cancer. In line with this observation, loss-of-LKB1 rendered breast cancer cells highly migratory and invasive, attaining cancer stem cell-like phenotype. Accordingly, LKB1-null breast cancer cells exhibited an increased ability to form mammospheres and elevated expression of pluripotency-factors (Oct4, Nanog and Sox2), properties also observed in spontaneous tumors in Lkb1(-/-) mice...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28580793/rationale-and-protocol-of-metnet-2-trial-lanreotide-autogel-plus-metformin-in-advanced-gastrointestinal-or-lung-neuroendocrine-tumors
#16
Sara Pusceddu, Natalie Prinzi, Giuseppe Lo Russo, Daniela Femia, Massimo Milione, Federica Perrone, Elena Tamborini, Laura Concas, Iolanda Pulice, Claudio Vernieri, Francesca Corti, Roberto Buzzoni, Filippo de Braud
Metformin (MET) has recently emerged as a potentially active agent in cancer prevention and treatment. MET is thought to exert its antitumor effects either via modification of systemic metabolism or through cell-autonomous effects (e.g., activation of AMPK and inhibition of the mTOR pathway). Preliminary findings of the PRIME-NET study suggest that the addition of MET to treatment with everolimus (EVE) and/or somatostatin analogs (SSAs) can provide clinical benefit in diabetic neuroendocrine tumor (NET) patients...
June 5, 2017: Future Oncology
https://www.readbyqxmd.com/read/28574837/6-mercaptopurine-promotes-energetic-failure-in-proliferating-t-cells
#17
Ana A Fernández-Ramos, Catherine Marchetti-Laurent, Virginie Poindessous, Samantha Antonio, Pierre Laurent-Puig, Sylvie Bortoli, Marie-Anne Loriot, Nicolas Pallet
The anticancer drug 6-mercaptopurine (6-MP) inhibits de novo purine synthesis and acts as an antiproliferative agent by interfering with protein, DNA and RNA synthesis and promoting apoptosis. Metabolic reprogramming is crucial for tumor progression to foster cancer cells growth and proliferation, and is regulated by mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) as well as the oncogenes Myc and hypoxia inducible factor 1α (HIF-1α). We hypothesized that 6-MP impacts metabolic remodeling through its action on nucleotide synthesis...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566623/moutan-cortex-protects-hepatocytes-against-oxidative-injury-through-amp-activated-protein-kinase-pathway
#18
Mi Hee Jang, Kwang-Youn Kim, Phil Hyun Song, Su Youn Baek, Hye Lim Seo, Eun Hye Lee, Suel-Gi Lee, Kwang Il Park, Soon-Cheol Ahn, Sang Chan Kim, Young Woo Kim
Moutan Cortex, the root bark of Paeonia suffruticosa ANDREWS in Ranunculaceae, has widely demonstrated analgesic, anti-spasmodic, and anti-inflammatory effects in various cancer and immune cell lines. Oxidative stress is associated with development of several diseases, including liver disease. We prepared the water extract of Moutan Cortex (MCE) to investigate the cytoprotective activities and its mechanism. MCE protected hepatocytes from arachidonic acid (AA)+iron induced oxidative stress, as indicated by reactive oxygen species (ROS) production and cell viability analysis...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28562331/dual-degradation-signals-destruct-gli1-ampk-inhibits-gli1-through-%C3%AE-trcp-mediated-proteasome-degradation
#19
Rui Zhang, Sherri Y Huang, Kay Ka-Wai Li, Yen-Hsing Li, Wei-Hsuan Hsu, Guang Jun Zhang, Chun-Ju Chang, Jer-Yen Yang
Overexpression of the GLI1 gene has frequently been found in various cancer types, particularly in brain tumors, in which aberrant GLI1 induction promotes cancer cell growth. Therefore, identifying the molecular players controlling GLI1 expression is of clinical importance. Previously, we reported that AMPK directly phosphorylated and destabilized GLI1, resulting in the suppression of the Hedgehog signaling pathway. The current study not only demonstrates that AMPK inhibits GLI1 nuclear localization, but further reveals that β-TrCP plays an essential role in AMPK-induced GLI1 degradation...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549345/a-novel-synthetic-derivative-of-quercetin-8-trifluoromethyl-3-5-7-3-4-o-pentamethyl-quercetin-inhibits-bladder-cancer-growth-by-targeting-the-ampk-mtor-signaling-pathway
#20
Ting Tao, Caimei He, Jun Deng, Yanjun Huang, Qiongli Su, Mei Peng, Meiling Yi, Kwame Oteng Darko, Hui Zou, Xiaoping Yang
Quercetin is a naturally existing compound and shows attractive anticancer properties for a variety of solid tumors including glioma, bladder cancer, hepatocellular carcinoma, breast cancer, hematological malignancies and prostate carcinoma. However, these anticancer properties have not been clinically approved due to unclear mechanistic information and its low bioactivity. In our previous study, we elucidated that quercetin activates AMPK pathway which is the major mechanism for its unique anticancer effect in bladder cancer...
May 11, 2017: Oncotarget
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