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https://www.readbyqxmd.com/read/28808415/foxo-signaling-pathways-as-therapeutic-targets-in-cancer
#1
REVIEW
Mohd Farhan, Haitao Wang, Uma Gaur, Peter J Little, Jiangping Xu, Wenhua Zheng
Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28799249/opposing-effects-on-cardiac-function-by-calorie-restriction-in-different-aged-mice
#2
Yunlu Sheng, Shan Lv, Min Huang, Yifan Lv, Jing Yu, Juan Liu, Tingting Tang, Hanmei Qi, Wenjuan Di, Guoxian Ding
Calorie restriction (CR) increases average and maximum lifespan and exhibits an apparent beneficial impact on age-related diseases. Several studies have shown that CR initiated either in middle or old age could improve ischemic tolerance and rejuvenate the aging heart; however, the data are not uniform when initiated in young. The accurate time to initiate CR providing maximum benefits for cardiac remodeling and function during aging remains unclear. Thus, whether a similar degree of CR initiated in mice of different ages could exert a similar effect on myocardial protection was investigated in this study...
August 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/28794203/the-myst-family-histone-acetyltransferase-complex-regulates-stress-resistance-and-longevity-through-transcriptional-control-of-daf-16-foxo-transcription-factors
#3
Takako Ikeda, Masaharu Uno, Sakiko Honjoh, Eisuke Nishida
The well-known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS-1/TRR-1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans Our results show that these beneficial effects are largely mediated through transcriptional up-regulation of the FOXO transcription factor DAF-16...
August 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28783736/glutamate-alleviates-muscle-protein-loss-by-modulating-tlr4-nods-akt-foxo-and-mtor-signaling-pathways-in-lps-challenged-piglets
#4
Ping Kang, Xiuying Wang, Huanting Wu, Huiling Zhu, Yongqing Hou, Longmei Wang, Yulan Liu
The experiment was conducted to study the effect of the glutamate (Glu) on muscle protein loss through toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain proteins (NODs), Akt/Forkhead Box O (Akt/FOXO) and mammalian target of rapamycin (mTOR) signaling pathways in LPS-challenged piglets. Twenty-four weaned piglets were assigned into four treatments: (1) Control; (2) LPS+0% Glu; (3) LPS + 1.0% Glu; (4) LPS + 2.0% Glu. The experiment was lasted for 28 days. On d 28, the piglets in the LPS challenged groups were injected with LPS on 100 μg/kg body weight (BW), and the piglets in the control group were injected with the same volume of 0...
2017: PloS One
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#5
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Diabetic heart pathology has a serious social impact due to high prevalence worldwide and significant mortality/invalidation of diabetic patients suffered from cardiomyopathy. The pathogenesis of diabetic and diabetes-related cardiomyopathy is associated with progressive loss and impairment of cardiac function due to adverse effects of metabolic, prooxidant, proinflammatory, and pro-apoptotic stress factors. In the adult heart, the transcriptional factor forkhead box-1 (FOXO-1) is involved in maintaining cardiomyocytes in the homeostatic state and induction of their adaptation to metabolic and pro-oxidant stress stimuli...
August 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28775361/a-conserved-neuronal-daf-16-foxo-plays-an-important-role-in-conveying-pheromone-signals-to-elicit-repulsion-behavior-in-caenorhabditis-elegans
#6
Donha Park, Jeong-Hoon Hahm, Saeram Park, Go Ha, Gyeong-Eon Chang, Haelim Jeong, Heekyeong Kim, Sunhee Kim, Eunji Cheong, Young-Ki Paik
Animals use pheromones as a conspecific chemical language to respond appropriately to environmental changes. The soil nematode Caenorhabditis elegans secretes ascaroside pheromones throughout the lifecycle, which influences entry into dauer phase in early larvae, in addition to sexual attraction and aggregation. In adult hermaphrodites, pheromone sensory signals perceived by worms usually elicit repulsion as an initial behavioral signature. However, the molecular mechanisms underlying neuronal pheromone sensory process from perception to repulsion in adult hermaphrodites remain poorly understood...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#7
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28774833/foxo-in-b-cell-lymphopoiesis-and-b-cell-neoplasia
#8
REVIEW
Alexey Ushmorov, Thomas Wirth
FOX O family transcription factors are important for differentiation and function of multiple cell types. In B lymphocytes they play a critical role. The activity of FOXOs is directly regulated both by signaling from B cell receptor (BCR) and cytokine receptors. FOXO1 action controls the transition between differentiation stages of B cell development. In comparison to other FOXO family members, FOXO1 plays a superior role in the regulation of early stages of B-cell differentiation. Although being known as a negative regulator of cell proliferation and therefore potential tumor suppressor, FOXO1 is downregulated only in Hodgkin lymphoma (HL) subtypes...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28771227/klotho-enhances-foxo3-mediated-manganese-superoxide-dismutase-expression-by-negatively-regulating-pi3k-akt-pathway-during-tacrolimus-induced-oxidative-stress
#9
Sun Woo Lim, Long Jin, Kang Luo, Jian Jin, Yoo Jin Shin, Sung Yi Hong, Chul Woo Yang
Mammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28770437/comparing-the-effects-of-melatonin-with-caloric-restriction-in-the-hippocampus-of-aging-mice-involvement-of-sirtuin1-and-the-foxos-pathway
#10
Anorut Jenwitheesuk, Seongjoon Park, Prapimpun Wongchitrat, Jiraporn Tocharus, Sujira Mukda, Isao Shimokawa, Piyarat Govitrapong
It has been suggested that age-related neurodegeneration might be associated with neuropeptide Y (NPY); sirtuin1 (SIRT1) and forkhead box transcription factors O subfamily (FOXOs) pathways. Melatonin, a hormone mainly secreted by the pineal gland, is another anti-aging agent associated with the SIRT1-FOXOs pathway. This study aimed to compare the effects of melatonin (Mel) and caloric restriction (CR) on the expression of Sirt1, FoxO1, FoxO3a and FOXOs target genes in the aging mouse hippocampus. Neuropeptide Y-knockout (NpyKO) and wild-type (WT) male mice aged 19 months were previously treated either with food ad libitum or CR for 16 months...
August 2, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28766017/pmk-1-p38-mapk-promotes-cadmium-stress-resistance-the-expression-of-skn-1-nrf-and-daf-16-target-genes-and-protein-biosynthesis-in-caenorhabditis-elegans
#11
Alex Keshet, Ansgar Mertenskötter, Sarah A Winter, Vanessa Brinkmann, Ramona Dölling, Rüdiger J Paul
The mechanisms of cadmium (Cd) resistance are complex and not sufficiently understood. The present study, therefore, aimed at assessing the roles of important components of stress-signaling pathways and of ABC transporters under severe Cd stress in Caenorhabditis elegans. Survival assays on mutant and control animals revealed a significant promotion of Cd resistance by the PMK-1 p38 MAP kinase, the transcription factor DAF-16/FoxO, and the ABC transporter MRP-1. Transcriptome profiling by RNA-Seq on wild type and a pmk-1 mutant under control and Cd stress conditions revealed, inter alia, a PMK-1-dependent promotion of gene expression for the translational machinery...
August 1, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28761622/flavonoids-as-putative-inducers-of-the-transcription-factors-nrf2-foxo-and-ppar%C3%AE
#12
Kathrin Pallauf, Nils Duckstein, Mario Hasler, Lars-Oliver Klotz, Gerald Rimbach
Dietary flavonoids have been shown to extend the lifespan of some model organisms and may delay the onset of chronic ageing-related diseases. Mechanistically, the effects could be explained by the compounds scavenging free radicals or modulating signalling pathways. Transcription factors Nrf2, FoxO, and PPARγ possibly affect ageing by regulating stress response, adipogenesis, and insulin sensitivity. Using Hek-293 cells transfected with luciferase reporter constructs, we tested the potency of flavonoids from different subclasses (flavonols, flavones, flavanols, and isoflavones) to activate these transcription factors...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28750751/the-anti-aging-and-anti-oxidation-effects-of-tea-water-extract-in-caenorhabditis-elegans
#13
Tianyi Fei, Jian Fei, Fang Huang, Tianpei Xie, Jifeng Xu, Yi Zhou, Ping Yang
Tea includes puer tea, black tea, green tea and many others. By using model organism Caenorhabditis elegans, the anti-aging and anti-oxidation effects of tea water extract were systemically examined in this study. We found that water extract of puer tea, black tea and green tea all increased the lifespan of worms, postponed Aβ-induced progressive paralysis in Alzheimer's disease transgenic worms, and improved the tolerance of worms to the oxidative stress induced by heavy metal Cr(6+). Moreover, the anti-oxidation effects of tea water extract at low concentration were different among 4 kinds of brands of green tea...
July 24, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28749975/circulating-micrornas-and-association-with-methacholine-pc20-in-the-childhood-asthma-management-program-camp-cohort
#14
Joshua S Davis, Maoyun Sun, Alvin T Kho, Kip G Moore, Jody M Sylvia, Scott T Weiss, Quan Lu, Kelan G Tantisira
INTRODUCTION: Circulating microRNAs (miRNA) are promising biomarkers for human diseases. Our study hypothesizes that circulating miRNA would reveal candidate biomarkers related to airway hyperresponsiveness (AHR) and provide biologic insights into asthma epigenetic influences. METHODS: Serum samples obtained at randomization for 160 children in the Childhood Asthma Management Program were profiled using a TaqMan miRNA array set. The association of the isolated miRNA with methacholine PC20 was assessed...
2017: PloS One
https://www.readbyqxmd.com/read/28744398/kinase-inhibitors-of-her2-akt-pathway-induce-erk-phosphorylation-via-a-foxo-dependent-feedback-loop
#15
Smita Matkar, Chiying An, Xianxin Hua
Inhibitors of the HER2/PI3K/AKT pathway are being developed, and shown promise in clinical trials for various types of cancers. However, development of drug resistance is a challenging problem for therapy. Elucidating various adaptive pathways leading to resistance or reduced sensitivity to drugs targeting the HER2/PI3K/AKT pathway may provide new insights into countering the resistance. Epidermal growth factor receptor (EGFR, aka HER1), which can dimerize with HER2, can activate a cascade consisting of Ras/RAF/MEK/ERK, promoting tumorigenesis...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#16
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28732359/resveratrol-inhibits-age-dependent-spontaneous-tumorigenesis-by-sirt1-mediated-post-translational-modulations-in-the-annual-fish-nothobranchius-guentheri
#17
Tingting Liu, Long Ma, Zhaodi Zheng, Fenglin Li, Shan Liu, Yingbo Xie, Guorong Li
Resveratrol, SIRT1 activator, inhibits carcinogenesis predominantly performed in transgenic animal models, orthotopic cancers of nude mice or different cancer cell lines, but its effects during process of spontaneous tumors using vertebrate models remain untested. Spontaneous liver neoplasm is an age-related disease and is inhibited by resveratrol in the annual fish Nothobranchius guentheri, which indicates that the fish can act as an excellent model to study spontaneous tumorigenesis. Totally, 175 fish were fed with resveratrol and another 175 fish for controls...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28719355/mirna-223-suppresses-foxo1-and-functions-as-a-potential-tumor-marker-in-breast-cancer
#18
Y-T Wei, D-W Guo, X-Z Hou, D-Q Jiang
Breast cancer is the most commonly diagnosed cancer in women and a leading cause of cancer mortality. MicroRNAs (miRNAs) have been found to play a key role in proliferation, metastasis and invasion of cancer. In previous study, we found that miRNA-223 was significant expression inexosome derived from peripheral blood serum of breast cancer patients than in samples from control subjects, Therefor,the role ofmiRNA-223willbe researched in MCF-7 breast cancer cells.In this study, to explore the role of miRNA-223in influencing cell proliferation, metastasis and invasion of breast cancer, TargetScan tools (http://www...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28713921/anti%C3%A2-lung-cancer-effect-of-glucosamine-by-suppressing-the-phosphorylation-of-foxo
#19
Zhanwu Yu, Yinghua Ju, Hongxu Liu
Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712871/inhibition-of-phosphatidylinositide-3-kinase-ameliorates-antiproliferation-by-benzyl-isothiocyanate-in-human-colon-cancer-cells
#20
Xiaoyang Liu, Chiaki Takano, Tomomi Shimizu, Shintaro Yokobe, Naomi Abe-Kanoh, Beiwei Zhu, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura
In the present study, we clarified the role of phosphatidylinositide 3-kinase (PI3K) in antiproliferation induced by benzyl isothiocyanate (BITC) in human colorectal cancer cells. BITC simultaneously activated the PI3K/Akt/forkhead box O (FoxO) pathway, whereas it significantly inhibited the proliferation in human colorectal cancer cells. Inhibitory experiments using a PI3K selective inhibitor, LY294002 or NVP-BEZ235, significantly enhanced the BITC-induced antiproliferation and apoptotic cell population with the attenuation of the BITC-induced activation of the PI3K/Akt/FoxO survival pathway...
July 13, 2017: Biochemical and Biophysical Research Communications
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