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https://www.readbyqxmd.com/read/28901472/inositol-hexaphosphate-hydrolysate-competitively-binds-to-akt-to-inhibit-the-proliferation-of-colon-carcinoma
#1
Chen Chen, Fuguo Yang, Cuiping Liu, Lianhua Cui, Min Fu, Yang Song
Phytate, myto-inositol 1,2,3,4,5,6 hexaphosphate (IP6), is recognized as an anti-nutrition phytochemical for decades. Recently, numerous studies have indicated that IP6 and its hydrolysates could suppress colon oncogenesis. However, very little is known concerning the mechanism of IP6 hydrolysates in regulating colon oncogenesis. The aim of the present study was to identify the underlying relationship between IP6 hydrolysates and colon cancer. Three types of human colorectal cancer cells were utilized in the present study...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28891094/regulation-of-the-tumor-suppressor-pten-by-natural-anticancer-compounds
#2
REVIEW
Do-Hee Kim, Jinyoung Suh, Young-Joon Surh, Hye-Kyung Na
The tumor suppressor phosphatase and tensin homologue (PTEN) has phosphatase activity, with phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a product of phosphatidylinositol 3-kinase (PI3K), as one of the principal substrates. PTEN is a negative regulator of the Akt pathway, which plays a fundamental role in controlling cell growth, survival, and proliferation. Loss of PTEN function has been observed in many different types of cancer. Functional inactivation of PTEN as a consequence of germ-line mutations or promoter hypermethylation predisposes individuals to malignancies...
August 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28877984/%C3%AE-5%C3%AE-1-integrinpromotes-tension-dependent-mammary-epithelial-cell-invasion-by-engaging-the-fibronectin-synergy-site
#3
Y A Miroshnikova, G I Rozenberg, L Cassereau, M Pickup, J K Mouw, G Ou, K L Templeman, I Elloumi-Hannachi, K Gooch, A L Sarang-Sieminski, A J García, V M Weaver
Tumors are fibrotic and characterized by abundant, remodeled and cross-linked collagen that stiffens the extracellular matrix stroma. The stiffened collagenous stroma fosters malignant transformation of the tissue by increasing tumor cell tension to promote focal adhesion formation and potentiate growth factor receptor signaling through ERK and PI3 kinase. Importantly, collagen cross-linking requires fibronectin. Fibrotic tumors contain abundant fibronectin and tumor cells frequently up regulate the fibronectin receptor α5β1 integrin...
September 6, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28842595/regulation-of-hgf-induced-hepatocyte-proliferation-by-the-small-gtpase-arf6-through-the-pip2-producing-enzyme-pip5k1a
#4
Meng-Tsz Tsai, Naohiro Katagiri, Norihiko Ohbayashi, Kenichi Iwasaki, Nobuhiro Ohkohchi, Shih-Torng Ding, Yasunori Kanaho, Yuji Funakoshi
HGF and its receptor c-Met are critical molecules in various biological processes. Others and we have previously shown that the small GTPase Arf6 plays a pivotal role in HGF signaling in hepatocytes. However, the molecular mechanism of how Arf6 regulates HGF signaling is unclear. Here, we show that Arf6 plays an important role in HGF-stimulated hepatocyte proliferation and liver regeneration through the phosphatidylinositol 4,5-bisphosphate (PIP2)-producing enzyme PIP5K1A. We find that knockdown of Arf6 and PIP5K1A in HepG2 cells inhibits HGF-stimulated proliferation, Akt activation, and generation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and its precursor PIP2...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28803992/p-rex1-amplification-promotes-progression-of-cutaneous-melanoma-via-the-pak1-p38-mmp-2-pathway
#5
Jinhua Wang, Hajime Hirose, Guanhua Du, Kelly Chong, Eiji Kiyohara, Isaac P Witz, Dave S B Hoon
P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN...
October 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28774345/determination-of-optimized-oxygen-partial-pressure-to-maximize-the-liver-regenerative-potential-of-the-secretome-obtained-from-adipose-derived-stem-cells
#6
Sang Chul Lee, Kee-Hwan Kim, Ok-Hee Kim, Sang Kuon Lee, Ha-Eun Hong, Seong Su Won, Sang-Jin Jeon, Byung Jo Choi, Wonjun Jeong, Say-June Kim
BACKGROUND: A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO2) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined. METHODS: We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO2 (21%, 10%, 5%, and 1%)...
August 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28771726/annexin-a2-positively-regulates-milk-synthesis-and-proliferation-of-bovine-mammary-epithelial-cells-through-the-mtor-signaling-pathway
#7
Minghui Zhang, Dongying Chen, Zhen Zhen, Jinxia Ao, Xiaohan Yuan, Xuejun Gao
Annexin A2 (AnxA2) has been shown to play multiple roles in growth, development and metabolism, but the functions of AnxA2 and the signaling pathways associated with AnxA2 are still not fully understood. In this study, we aim to reveal whether and how AnxA2 could be involved in milk synthesis and proliferation of bovine mammary epithelial cells (BMECs). Using gene function study approaches, we found that AnxA2 positively regulates PIP3 level, phosphorylation of mTOR and protein levels of SREBP-1c and Cyclin D1 leading to milk synthesis and cell proliferation...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28729453/pi3k-and-calcium-signaling-in-cardiovascular-disease
#8
REVIEW
Alessandra Ghigo, Muriel Laffargue, Mingchuan Li, Emilio Hirsch
Receptor signaling relays on intracellular events amplified by secondary and tertiary messenger molecules. In cardiomyocytes and smooth muscle cells, cyclic AMP (cAMP) and subsequent calcium (Ca(2+)) fluxes are the best characterized receptor-regulated signaling events. However, most of receptors able to modify contractility and other intracellular responses signal through a variety of other messengers, and whether these signaling events are interconnected has long remained unclear. For example, the PI3K (phosphoinositide 3-kinase) pathway connected to the production of the lipid second messenger PIP3/PtdIns(3,4,5)P3 (phosphatidylinositol (3,4,5)-trisphosphate) is potentially involved in metabolic regulation, activation of hypertrophy, and survival pathways...
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28714121/acetylcholine-dependent-upregulation-of-task-1-channels-in-thalamic-interneurons-by-a-smooth-muscle-like-signalling-pathway
#9
Michael Leist, Susanne Rinné, Maia Datunashvili, Ania Aissaoui, Hans-Christian Pape, Niels Decher, Sven G Meuth, Thomas Budde
KEY POINTS: The ascending brainstem transmitter acetylcholine depolarizes thalamocortical relay neurons while it induces hyperpolarization in local circuit inhibitory interneurons. Sustained K(+) currents are modulated in thalamic neurons to control their activity modes; for the interneurons the molecular nature of the underlying ion channels is as yet unknown. Activation of TASK-1 K(+) channels results in hyperpolarization of interneurons and suppression of their action potential firing...
September 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28701424/more-than-a-mere-supply-of-monomers-g-actin-pools-regulate-actin-dynamics-in-dendritic-spines
#10
Katalin Schlett
Synaptic activity reshapes the morphology of dendritic spines via regulating F-actin arborization. In this issue, Lei et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612042) reports a novel, G-actin-dependent regulation of actin polymerization within spine heads. They show that actin monomer levels are elevated in spines upon activity, with G-actin immobilized by the local enrichment of phosphatidylinositol (3,4,5)-triphosphate (PIP3) within the spine plasma membrane.
August 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28687663/a-module-for-rac-temporal-signal-integration-revealed-with-optogenetics
#11
Brian R Graziano, Delquin Gong, Karen E Anderson, Anne Pipathsouk, Anna R Goldberg, Orion D Weiner
Sensory systems use adaptation to measure changes in signaling inputs rather than absolute levels of signaling inputs. Adaptation enables eukaryotic cells to directionally migrate over a large dynamic range of chemoattractant. Because of complex feedback interactions and redundancy, it has been difficult to define the portion or portions of eukaryotic chemotactic signaling networks that generate adaptation and identify the regulators of this process. In this study, we use a combination of optogenetic intracellular inputs, CRISPR-based knockouts, and pharmacological perturbations to probe the basis of neutrophil adaptation...
August 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28636047/decoding-the-regulatory-mechanism-of-glucose-and-insulin-induced-phosphatidylinositol-3-4-5-trisphosphate-dynamics-in-%C3%AE-cells
#12
Tagari Samanta, Peeyush Sharma, Dwijendra Kukri, Sandip Kar
In MIN6 pancreatic β-cells, glucose and insulin act in a synergistic manner to regulate the dynamics of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3). However, the precise regulatory mechanism behind such an experimentally observed synergy is poorly understood. In this article, we propose a phenomenological mathematical model for studying the glucose and insulin driven PIP3 activation dynamics under various stimulatory conditions to unfold the mechanism responsible for the observed synergy. The modeling study reveals that the experimentally observed oscillation in PIP3 dynamics with disparate time scales for different external glucose doses is mainly orchestrated by the complex dynamic regulation of cytosolic Ca(2+) in β-cells...
July 25, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#13
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28628306/lysine-deacetylation-by-hdac6-regulates-the-kinase-activity-of-akt-in-human-neural-progenitor-cells
#14
Jonathan Iaconelli, Jasmin Lalonde, Bradley Watmuff, Bangyan Liu, Ralph Mazitschek, Stephen J Haggarty, Rakesh Karmacharya
The AKT family of serine-threonine kinases functions downstream of phosphatidylinositol 3-kinase (PI3K) to transmit signals by direct phosphorylation of a number of targets, including the mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), and β-catenin. AKT binds to phosphatidylinositol (3,4,5)-triphosphate (PIP3) generated by PI3K activation, which results in its membrane localization and subsequent activation through phosphorylation by phosphoinositide-dependent protein kinase 1 (PDK1)...
July 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28547571/clinical-presentations-and-molecular-studies-of-invasive-renal-epithelioid-angiomyolipoma
#15
Cheng-Keng Chuang, Hsin Chia Angela Lin, Han-Yu Tasi, Kun-Han Lee, Yuting Kao, Fukai Leo Chuang, Ying-Hsu Chang, Po-Hung Lin, Chung-Yi Liu, See-Tong Pang
PURPOSE: Epithelioid angiomyolipoma (EAML) is a rare variant of renal angiomyolipoma with malignant potential, and the cytogenetic and clinical behavior of EAML remains a challenging issue. METHODS: We retrospectively analyze the clinical courses of five EAML, the use of everolimus on metastatic EAML, and next-generation sequencing (NGS) and polymerase chain reaction (PCR) studies to investigate the gene mutation of TSC and the impact of PI3K/Akt/mTOR signaling pathway in metastatic EAML...
May 25, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28516764/an-autoinhibitory-role-for-the-pleckstrin-homology-domain-of-interleukin-2-inducible-tyrosine-kinase-and-its-interplay-with-canonical-phospholipid-recognition
#16
Sujan Devkota, Raji E Joseph, Scott E Boyken, D Bruce Fulton, Amy H Andreotti
Pleckstrin homology (PH) domains are well-known as phospholipid binding modules, yet evidence that PH domain function extends beyond lipid recognition is mounting. In this work, we characterize a protein binding function for the PH domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases. Its N-terminal PH domain is a well-characterized lipid binding module that localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP3) binding...
June 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28515318/molecular-mechanism-of-activation-of-class-ia-phosphoinositide-3-kinases-pi3ks-by-membrane-localized-hras
#17
COMPARATIVE STUDY
Braden D Siempelkamp, Manoj K Rathinaswamy, Meredith L Jenkins, John E Burke
Class IA PI3Ks are involved in the generation of the key lipid signaling molecule phosphatidylinositol 3,4,5-trisphosphate (PIP3), and inappropriate activation of this pathway is implicated in a multitude of human diseases, including cancer, inflammation, and primary immunodeficiencies. Class IA PI3Ks are activated downstream of the Ras superfamily of GTPases, and Ras-PI3K interaction plays a key role in promoting tumor formation and maintenance in Ras-driven tumors. Investigating the detailed molecular events in the Ras-PI3K interaction has been challenging because it occurs on a membrane surface...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28450917/diagnostic-value-of-high-frequency-color-doppler-ultrasonography-examination-in-combination-with-anti-cyclic-citrullinated-peptide-antibody-testing-in-rheumatoid-arthritis-patients
#18
Ming-Yu Wang, Xian-Bin Wang, Xue-Hui Sun, Feng-Li Liu, Sheng-Chuan Huang
We studied the diagnostic value of high-frequency color Doppler ultrasonography (HCDU) examination in combination with anti-cyclic citrullinated peptide (anti-CCP) antibody testing in rheumatoid arthritis (RA) patients with finger joint damage. From January 2015 to December 2015, 80 patients diagnosed with RA with finger joints damage were enrolled in this study. Patients were examined with HCDU. Serum anti-CCP antibody level was tested using ELISA, and results were compared with the healthy control group. Results obtained by ELISA demonstrated that the positive rate of anti-CCP antibodies was 73...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28445593/nr5a2-discovering-compounds-that-block-tumor-growth-in-pdac
#19
REVIEW
Robert Fletterick
Pancreatic cancers depend on driver molecules, oncogene proteins such as RAS. NR5A2 protein is a transcription factor and either activates or inhibits transcription through actions at hundreds of enhancers. It has unusual properties with effects appearing in multiple signaling networks. NR5A2 is a pluripotency reprogramming factor in the class nuclear receptor. Its controlling hormone is PIP3. Experiments suggest NR5A2 activation drives PDAC and inhibitors blunt cancer cell proliferation.
July 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28430130/timp1-promotes-cell-survival-by-activating-the-pdk1-signaling-pathway-in-melanoma
#20
Mariana Toricelli, Fabiana H M Melo, Aline Hunger, Daniela Zanatta, Bryan E Strauss, Miriam G Jasiulionis
High TIMP1 expression is associated with poor prognosis in melanoma, where it can bind to CD63 and β1 integrin, inducing PI3-kinase pathway and cell survival. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), generated under phosphatidylinositol-3-kinase (PI3K) activation, enables the recruitment and activation of protein kinase B (PKB/AKT) and phosphoinositide-dependent kinase 1 (PDK1) at the membrane, resulting in the phosphorylation of a host of other proteins. Using a melanoma progression model, we evaluated the impact of Timp1 and AKT silencing, as well as PI3K, PDK1, and protein kinase C (PKC) inhibitors on aggressiveness characteristics...
April 21, 2017: Cancers
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