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https://www.readbyqxmd.com/read/29150352/dysregulation-of-mrna-translation-and-energy-metabolism-in-cancer
#1
REVIEW
Matthew Leibovitch, Ivan Topisirovic
Dysregulated mRNA translation and aberrant energy metabolism are frequent in cancer. Considering that mRNA translation is an energy demanding process, cancer cells must produce sufficient ATP to meet energy demand of hyperactive translational machinery. In recent years, the mammalian/mechanistic target of rapamycin (mTOR) emerged as a central regulatory node which coordinates energy consumption by the translation apparatus and ATP production in mitochondria. Aberrant mTOR signaling underpins the vast majority of cancers whereby increased mTOR activity is thought to be a major determinant of both malignant translatomes and metabolomes...
November 2, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29150317/amp-activated-protein-kinase-regulation-of-the-nlrp3-inflammasome-during-aging
#2
REVIEW
Mario D Cordero, Matthew R Williams, Bernhard Ryffel
The NLRP3 inflammasome has recently emerged as an unexpected marker of stress and metabolic risk and has also been implicated in the development of major aging-related diseases such as gout, type 2 diabetes, obesity, cancer, and neurodegenerative and cardiovascular disorders. Several pathways regulating the NLRP3 inflammasome are currently being studied, but how the NLRP3 inflammasome is regulated remains unknown. AMP-activated protein kinase (AMPK), a central regulator of multiple metabolic pathways involved in the pathophysiology of aging and age-related diseases, has emerged as an important integrator of signals controlling inflammation including the inflammasome...
November 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29140069/dual-functions-of-cyclometalated-iridium-iii-complexes-anti-metastasis-and-lysosome-damaged-photodynamic-therapy
#3
Fang-Xin Wang, Mu-He Chen, Yan-Nan Lin, Hang Zhang, Cai-Ping Tan, Liang-Nian Ji, Zongwan Mao
Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can inhibit several cancerous processes including cell migration, invasion, colony formation and angiogenesis effectively. Interestingly, they show much higher singlet oxygen quantum yield in acidic solution than in neutral solution. Upon irradiation at 425 nm with low energy (1.2 J·cm(-2)), they can induce apoptosis through lysosomal damage, evaluation of ROS level and activation of caspase-3/7...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29138862/liver-kinase%C3%A2-b1-restoration-promotes-exosome-secretion-and-motility-of-lung-cancer-cells
#4
Cheng Zhang, Xiang Xiao, Minyi Chen, Hitham Aldharee, Yanfang Chen, Weiwen Long
Liver kinase B1 (LKB1) regulates a variety of cellular functions, including cell polarity, energy metabolism and cell growth, by targeting multiple signaling pathways such as AMPK/mTOR and p53. LKB1 functions as a tumor suppressor in sporadic cancers including lung cancer. Extracellular vesicles such as exosomes secreted by cancer cells modulate the tumor microenvironment and progression by targeting both tumor cells (autocrine actions) and other types of cells associated with tumors (paracrine actions). While the roles of LKB1 in cellular signaling in general is well-studied, its specific role in exosome-mediated signaling remains to be explored...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29137348/reverse-phase-protein-array-rppa-combined-with-computational-analysis-to-unravel-relevant-prognostic-factors-in-non-small-cell-lung-cancer-nsclc-a-pilot-study
#5
Vienna Ludovini, Rita Chiari, Lorenzo Tomassoni, Chiara Antonini, Elisa Baldelli, Sara Baglivo, Annamaria Siggillino, Francesca Romana Tofanetti, Guido Bellezza, K Alex Hodge, Emanuel Petricoin, Mariaelena Pierobon, Lucio Crinò, Fortunato Bianconi
In this work high throughput technology and computational analysis were used to study two stage IV lung adenocarcinoma patients treated with standard chemotherapy with markedly different survival (128 months vs 6 months, respectively) and whose tumor samples exhibit a dissimilar protein activation pattern of the signal transduction. Tumor samples of the two patients were subjected to Reverse Phase Protein Microarray (RPPA) analysis to explore the expression/activation levels of 51 signaling proteins. We selected the most divergent proteins based on the ratio of their RPPA values in the two patients with short (s-OS) and long (l-OS) overall survival (OS) and tested them against a EGFR-IGF1R mathematical model...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137114/natural-cyclopeptide-ra-xii-a-new-autophagy-inhibitor-suppresses-protective-autophagy-for-enhancing-apoptosis-through-ampk-mtor-p70s6k-pathways-in-hepg2-cells
#6
Lihua Song, Zhe Wang, Yurong Wang, Di Guo, Jianhong Yang, Lijuan Chen, Ninghua Tan
Liver cancer is a progressive, irreversible and aggressive malignant disease, which has no effective chemotherapeutic drugs. RA-XII, a natural cyclopeptide isolated from the traditional Chinese medicine Rubia yunnanensis, exerts anti-cancer and anti-inflammatory activities. This work aimed to investigate the effects of RA-XII on a hepatic tumor and its underlying mechanisms in human hepatoma HepG2 cells. The results showed that RA-XII effectively inhibited the proliferation of HepG2 cells. Consistently, RA-XII significantly induced apoptosis in HepG2 cells by decreasing the expression of caspase 3, 8, 9, and promoting the Cleavage of PARP...
November 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29133590/genotoxic-damage-activates-the-ampk-%C3%AE-1-isoform-in-the-nucleus-via-ca2-camkk2-signaling-to-enhance-tumor-cell-survival
#7
Diana Vara Ciruelos, Madhumita Dandapani, Alexander Gray, Ejaife O Egbani, A Mark Evans, D Grahame Hardie
Many genotoxic cancer treatments activate AMP-activated protein kinase (AMPK), but the mechanisms of AMPK activation in response to DNA damage, and its downstream consequences, have been unclear. In this study, etoposide activates the α1 but not the α2 isoform of AMPK, primarily within the nucleus. AMPK activation is independent of ataxia-telangiectasia mutated (ATM), a DNA damage-activated kinase, and the principal upstream kinase for AMPK, LKB1, but correlates with increased nuclear Ca2+ and requires the Ca2+/calmodulin-dependent kinase, CaMKK2...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133053/synthesis-and-biological-evaluation-of-new-berberine-derivatives-as-cancer-immunotherapy-agents-through-targeting-ido1
#8
Yan-Xiang Wang, Wei-Qiang Pang, Qing-Xuan Zeng, Zhe-Song Deng, Tian-Yun Fan, Jian-Dong Jiang, Hong-Bin Deng, Dan-Qing Song
To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty-five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure-activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial for potency. Among them, compounds 2f, 2i, 2n, 2o and 8b exhibited increased activities, with inhibition rate of 71-90% compared with BBR...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29130361/mta1-is-a-novel-regulator-of-autophagy-that-induces-tamoxifen-resistance-in-breast-cancer-cells
#9
Min-Ho Lee, Dahae Koh, Hyelin Na, Na-Lee Ka, Seungsu Kim, Hyeon-Ji Kim, Sungyoul Hong, Young Kee Shin, Je Kyung Seong, Mi-Ock Lee
Tamoxifen is commonly used to treat patients with ESR/ER-positive breast cancer, but its therapeutic benefit is limited by the development of resistance. Recently, alterations in macroautophagy/autophagy function were demonstrated to be a potential mechanism for tamoxifen resistance. Although MTA1 (metastasis-associated 1) has been implicated in breast tumorigenesis and metastasis, its role in endocrine resistance has not been studied. Here, we report that the level of MTA1 expression was upregulated in the tamoxifen resistant breast cancer cell lines MCF7/TAMR and T47D/TR, and knockdown of MTA1 sensitized the cells to 4-hydroxytamoxifen (4OHT)...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29127585/the-regulation-effect-of-ampk-in-immune-related-diseases
#10
REVIEW
Jing Wang, Zhenyu Li, Li Gao, Yanshuang Qi, Haibo Zhu, Xuemei Qin
AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays a key role in energetic metabolism regulation. Metabolic changes in immune cells, such as dendritic cell (DC), macrophages, neutrophils and lymphocytes that participate in the signal directed programs that promote or inhibit immune mediated diseases, including cancer, atherosclerosis and inflammatory diseases. Multiple pathogenic mechanisms are involved in the initiation and progression of disease, and many pathways have been uncovered...
November 8, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29121435/altered-intracellular-signaling-by-imatinib-increases-the-anti-cancer-effects-of-tyrosine-kinase-inhibitors-in-cml-cells
#11
Takuya Hirao, Masashi Yamaguchi, Megumi Kikuya, Hiroji Chibana, Kousei Ito, Shigeki Aoki
Tyrosine kinase inhibitors (TKIs), including imatinib (IM), improve the outcome of chronic myelogenous leukemia (CML) therapy. However, TKI treatment is long-term and can induce resistance to TKIs, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKIs...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29117108/effect-of-aicar-and-5-fluorouracil-on-x-ray-repair-cross-complementing-group-1-expression-and-consequent-cytotoxicity-regulation-in-human-hct-116-colorectal-cancer-cells
#12
Ko-Chao Lee, Chien-Tsong Lin, Shun-Fu Chang, Cheng-Nan Chen, Jing-Lan Liu, Wen-Shih Huang
Colorectal cancer (CRC) is one of the leading causes of cancer mortality and 5-Fluorouracil (5-FU) is the most common chemotherapy agent of CRC. A high level of X-ray repair cross complementing group 1 (XRCC1) in cancer cells has been associated with the drug resistance occurrence. Moreover, the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been indicated to regulate the cancer cell survival. Thus, this study was aimed to examine whether XRCC1 plays a role in the 5-FU/AMPK agonist (AICAR)-induced cytotoxic effect on CRC and the underlying mechanisms...
November 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29115548/frankincense-pine-needle-and-geranium-essential-oils-suppress-tumor-progression-through-the-regulation-of-the-ampk-mtor-pathway-in-breast-cancer
#13
Peng Ren, Xiang Ren, Lei Cheng, Lixin Xu
BC (BC), as the most common malignancy in women worldwide, is associated with high morbidity and mortality. However, chemoresistance and toxicity are the main causes that limit the success of treatment in aggressive BC cases. Thus, there is a vital need to identify and develop novel therapeutic agents. Frankincense, pine needle and geranium essential oils have been reported to play critical biological activities in cancer. However, to the best of our knowledge whether frankincense, pine needle and geranium essential oils have any effect on the progression of BC in MCF-7 cells remains unclear...
November 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29113354/6-phosphofructo-2-kinase-fructose-2-6-bisphosphatase-isoform-3-spatially-mediates-autophagy-through-the-ampk-signaling-pathway
#14
Siyuan Yan, Xiaoli Wei, Shanshan Xu, Hui Sun, Weijun Wang, Ling Liu, Xuejun Jiang, Yongxiang Zhang, Yongsheng Che
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), is a critical enzyme for glycolysis and highly expressed in cancer cells. It plays an essential role in regulating metabolism, angiogenesis, and inflammation. Although PFKFB3 is involved in modulating autophagy, its regulatory role appears to be either positive or negative, which remains to be clarified. Unlike other PFK-2/FBPase isoforms, PFKFB3 can localize in both nucleus and cytoplasm, leading to the speculation that subcellular localization of PFKFB3 may play a regulatory role in autophagy...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113214/ginkgolic-acid-inhibits-the-invasiveness-of-colon-cancer-cells-through-ampk-activation
#15
Lina Qiao, Jianbao Zheng, Xianzhen Jin, Guangbing Wei, Guanghui Wang, Xuejun Sun, Xuqi Li
Tumor cell invasion and metastasis are important processes in colorectal cancer that exert negative effects on patient outcomes; consequently, a prominent topic in the field of colorectal cancer study is the identification of safe and affordable anticancer drugs against cell invasion and metastasis, with limited side effects. Ginkgolic acid is a phenolic acid extracted from ginkgo fruit, ginkgo exotesta and ginkgo leaves. Previous studies have indicated that ginkgolic acid inhibits tumor growth and invasion in a number of types of cancer; however, limited studies have considered the effects of ginkgolic acid on colon cancer...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113067/omics-approaches-for-identifying-physiological-adaptations-to-genome-instability-in-aging
#16
REVIEW
Diletta Edifizi, Björn Schumacher
DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage...
November 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29110616/diallyl-disulfide-inhibits-breast-cancer-stem-cell-progression-and-glucose-metabolism-by-targeting-cd44-pkm2-ampk-signaling
#17
Xinhua Xie, Xiaojia Huang, Hailin Tang, Feng Ye, Lu Yang, Xiaofang Guo, Zhi Tian, Cheng Peng, Xiaoming Xie
It has been reported that diallyl disulfide (DADS) has anti-proliferative activity in many cancers. The purpose of this study was to investigate the functions of DADS and the underlying mechanisms of its effect in breast cancer stem cells (BCSCs). Mammosphere formation assay, glucose consumption assay, lactate production assay and mouse xenograft experiments were performed to explore the functions of DADS in BCSCs. ATPase activity assay, western blotting and immunohistochemistry (IHC) assay were conduct to explore the mechanisms underlying the effects of DADS in BCSCs...
October 24, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29106388/calcium-signalling-links-myc-to-nuak1
#18
T Monteverde, J Tait-Mulder, A Hedley, J R Knight, O J Sansom, D J Murphy
NUAK1 is a member of the AMPK-related family of kinases. Recent evidence suggests that NUAK1 is an important regulator of cell adhesion and migration, cellular and organismal metabolism, and regulation of TAU stability. As such, NUAK1 may play key roles in multiple diseases ranging from neurodegeneration to diabetes and metastatic cancer. Previous work revealed a crucial role for NUAK1 in supporting viability of tumour cells specifically when MYC is overexpressed. This role is surprising, given that NUAK1 is activated by the tumour suppressor LKB1...
November 6, 2017: Oncogene
https://www.readbyqxmd.com/read/29100319/berberine-and-cinnamaldehyde-together-prevent-lung-carcinogenesis
#19
Mingjing Meng, Shengnan Geng, Zhenhua Du, Jingjing Yao, Yaqiu Zheng, Zibo Li, Zhenzhen Zhang, Jiahuan Li, Yongjian Duan, Gangjun Du
Starving tumor cells by restricting nutrient sources is a promising strategy for combating cancer. Because both berberine and cinnamaldehyde can activate AMP-activated protein kinase (AMPK, a sensor of cellular energy status), we investigated whether the combination of berberine and cinnamaldehyde could synergistically prevent lung carcinogenesis through tumor cell starvation. Urethane treatment induced lung carcinogenesis in mice, downregulated AMPK and mammalian target of rapamycin (mTOR) while upregulating aquaporin-1 (AQP-1) and nuclear factor kappa B (NF-κB)...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100056/regulation-of-the-hippo-yap-pathway-by-glucose-sensor-o-glcnacylation
#20
Changmin Peng, Yue Zhu, Wanjun Zhang, Qinchao Liao, Yali Chen, Xinyuan Zhao, Qiang Guo, Pan Shen, Bei Zhen, Xiaohong Qian, Dong Yang, Jin-San Zhang, Dongguang Xiao, Weijie Qin, Huadong Pei
The Hippo pathway is crucial in organ size control and tissue homeostasis, with deregulation leading to cancer. An extracellular nutrition signal, such as glucose, regulates the Hippo pathway activation. However, the mechanisms are still not clear. Here, we found that the Hippo pathway is directly regulated by the hexosamine biosynthesis pathway (HBP) in response to metabolic nutrients. Mechanistically, the core component of Hippo pathway (YAP) is O-GlcNAcylated by O-GlcNAc transferase (OGT) at serine 109. YAP O-GlcNAcylation disrupts its interaction with upstream kinase LATS1, prevents its phosphorylation, and activates its transcriptional activity...
November 2, 2017: Molecular Cell
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