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https://www.readbyqxmd.com/read/28642362/regulation-of-rhoa-by-stat3-coordinates-glial-scar-formation
#1
Francois Renault-Mihara, Masahiko Mukaino, Munehisa Shinozaki, Hiromi Kumamaru, Satoshi Kawase, Matthieu Baudoux, Toshiki Ishibashi, Soya Kawabata, Yuichiro Nishiyama, Keiko Sugai, Kaori Yasutake, Seiji Okada, Masaya Nakamura, Hideyuki Okano
Understanding how the transcription factor signal transducer and activator of transcription-3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes...
June 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28641777/role-of-parl-pink1-parkin-pathway-in-adipocyte-differentiation
#2
Ming-Yuh Shiau, Pin-Shen Lee, Ying-Jyun Huang, Ching-Ping Yang, Chiao-Wan Hsiao, Kai-Yun Chang, Huan-Wen Chen, Yih-Hsin Chang
OBJECTIVE: Adipogenesis determines the number of adipocytes which is increased when individuals become obese. Mitochondria undergo remarkable morphological and functional changes during adipogenesis. PTEN-induced kinase 1 (PINK1) is pivotal to maintain mitochondrial homeostasis in neural cells. The present study aimed at investigating effects of PINK1 on adipogenesis and energy metabolism. METHODS: Expression of presenilin associated rhomboid-like protein (PARL), PINK1 and Parkin, as well as the interaction among these proteins was temporally examined during adipogenesis...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28641547/recent-advances-on-the-role-of-micrornas-in-both-insulin-resistance-and-cancer
#3
Adele Vivacqua, Paola De Marco, Antonino Belfiore, Marcello Maggiolini
BACKGROUND: Insulin resistance is a pathological condition characterized by the failure of target cells to uptake and metabolizes glucose in response to insulin. In particular, the elevated concentrations of glucose, insulin and free insulin growth factor-1, which result from insulin resistance, may generate a pro-inflammatory and pro-tumorigenic state. These alterations may underlie the increased risk to develop various types of cancer as well as the worse cancer prognosis observed in obese and diabetic patients...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641110/sox11-expression-promotes-regeneration-of-some-retinal-ganglion-cell-types-but-kills-others
#4
Michael W Norsworthy, Fengfeng Bei, Riki Kawaguchi, Qing Wang, Nicholas M Tran, Yi Li, Benedikt Brommer, Yiming Zhang, Chen Wang, Joshua R Sanes, Giovanni Coppola, Zhigang He
At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28640831/ribosomal-dna-copy-number-loss-and-sequence-variation-in-cancer
#5
Baoshan Xu, Hua Li, John M Perry, Vijay Pratap Singh, Jay Unruh, Zulin Yu, Musinu Zakari, William McDowell, Linheng Li, Jennifer L Gerton
Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28639901/downregulation-of-mir-193a-3p-inhibits-cell-growth-and-migration-in-renal-cell-carcinoma-by-targeting-pten
#6
Lingqi Liu, Yanqin Li, Shuchao Liu, Qixin Duan, Liang Chen, Tianpeng Wu, Huijun Qian, Sixing Yang, Dianqi Xin
Although miR-193a-3p has been found to be dysregulated in variety of human tumors, little is known about its role in renal cell carcinoma. This study was designed to investigate the function and underlying mechanism of miR-193a-3p in human renal cell carcinoma tissues and cell lines. Here, we demonstrated that the expression of miR-193-3p was increased in renal cell carcinoma tissues and cell lines. In addition, knockdown of miR-193a-3p significantly inhibited cell proliferation and colony formation and induced cells into G1 phase arrest...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28637716/modulation-of-plasma-metabolite-biomarkers-of-mapk-pathway-with-the-mek-inhibitor-ro4987655-pharmacodynamic-and-predictive-potential-in-metastatic-melanoma
#7
Joo Ern Ang, Akos Pal, Yasmin J Asad, Alan T Henley, Melanie Valenti, Gary Box, Alexis de Haven Brandon, Victoria Revell, Debra J Skene, Miro Venturi, Ruediger Rueger, Valerie Meresse, Suzanne A Eccles, Johann S de Bono, Stanley B Kaye, Paul Workman, Udai Banerji, Florence I Raynaud
<p>MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in preclinical models 21 plasma metabolites including amino acids, propionylcarnitine, phosphatidylcholines and sphingomyelins that were significantly altered in two B-RAF mutant melanoma xenografts and that were reversed following a single dose of the potent and selective MEK inhibitor RO4987655...
June 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28636948/pten%C3%AE-modulates-camkii-signaling-and-controls-contextual-fear-memory-and-spatial-learning
#8
Pan Wang, Fan Mei, Jiapan Hu, Minglu Zhu, Hailong Qi, Xi Chen, Ruiqi Li, Michael A McNutt, Yuxin Yin
PTEN (phosphatase and tensin homology deleted on chromosome 10) has multiple functions, and recent studies have shown that the PTEN family has isoforms. The roles of these PTEN family members in biologic activities warrant specific evaluation. Here, we show that PTENα maintains CaMKII in a state that is competent to induce long-term potentiation (LTP) with resultant regulation of contextual fear memory and spatial learning. PTENα binds to CaMKII with its distinctive N terminus and resets CaMKII to an activatable state by dephosphorylating it at sites T305/306...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636652/integrative-analysis-of-genomic-alterations-in-triple-negative-breast-cancer-in-association-with-homologous-recombination-deficiency
#9
Masahito Kawazu, Shinya Kojima, Toshihide Ueno, Yasushi Totoki, Hiromi Nakamura, Akiko Kunita, Wei Qu, Jun Yoshimura, Manabu Soda, Takahiko Yasuda, Natsuko Hama, Mihoko Saito-Adachi, Kazuhito Sato, Shinji Kohsaka, Eirin Sai, Masako Ikemura, Shigeru Yamamoto, Tomoko Ogawa, Masashi Fukayama, Keiichiro Tada, Yasuyuki Seto, Shinichi Morishita, Shoichi Hazama, Tatsuhiro Shibata, Yoshihiro Yamashita, Hiroyuki Mano
Triple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2. Currently, apart from poly ADP-ribose polymerase inhibitors, there are few effective therapeutic options for this type of cancer. Here, we present comprehensive characterization of the genetic alterations in TNBC performed by high coverage whole genome sequencing together with transcriptome and whole exome sequencing. Silencing of the BRCA1 gene impaired the homologous recombination pathway in a subset of TNBCs, which exhibited similar phenotypes to tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28631436/characterization-of-a-novel-p110%C3%AE-specific-inhibitor-bl140-that-overcomes-mdv3100-resistance-in-castration-resistant-prostate-cancer-cells
#10
Chenchen He, Shaofeng Duan, Liang Dong, Yifen Wang, Qingting Hu, Chunjing Liu, Marcus L Forrest, Jeffrey M Holzbeierlein, Suxia Han, Benyi Li
BACKGROUND: Our previous studies demonstrated that the class IA PI3K/p110β is critical in castration-resistant progression of prostate cancer (CRPC) and that targeting prostate cancer with nanomicelle-loaded p110β-specific inhibitor TGX221 blocked xenograft tumor growth in nude mice, confirming the feasibility of p110β-targeted therapy for CRPCs. To improve TGX221's aqueous solubility, in this study, we characterized four recently synthesized TGX221 analogs. METHODS: TGX221 analog efficacy were examined in multiple prostate cancer cell lines with the SRB cell growth assay, Western blot assay for AKT phosphorylation and cell cycle protein levels...
June 20, 2017: Prostate
https://www.readbyqxmd.com/read/28631420/expression-of-pten-long-mediated-by-crispr-cas9-can-repress-u87-cell-proliferation
#11
Na Fang, Tingxuan Gu, Yahui Wang, Shuzhen Wang, Fengling Wang, Yang An, Wenqiang Wei, Weijuan Zhang, Xiangqian Guo, Adil J Nazarali, Shaoping Ji
PTEN is a tumour suppressor that is frequently mutated in a variety of cancers. Hence, PTEN has significant potential as a therapeutic molecule. PTEN-long is an alternative translation variant, with an additional 173 amino acids added to the N-terminal of the canonical PTEN when CUG of the mRNA is utilized as the start codon. PTEN-long is secreted into serum and can re-enter cells throughout the body. One of the major barriers for gene therapy is to efficiently and specifically deliver DNA or RNA material to target cells...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28630945/the-icr96-exon-cnv-validation-series-a-resource-for-orthogonal-assessment-of-exon-cnv-calling-in-ngs-data
#12
Shazia Mahamdallie, Elise Ruark, Shawn Yost, Emma Ramsay, Imran Uddin, Harriett Wylie, Anna Elliott, Ann Strydom, Anthony Renwick, Sheila Seal, Nazneen Rahman
Detection of deletions and duplications of whole exons (exon CNVs) is a key requirement of genetic testing. Accurate detection of this variant type has proved very challenging in targeted next-generation sequencing (NGS) data, particularly if only a single exon is involved. Many different NGS exon CNV calling methods have been developed over the last five years. Such methods are usually evaluated using simulated and/or in-house data due to a lack of publicly-available datasets with orthogonally generated results...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28627671/downregulation-of-notch1-inhibits-the-invasion-and-metastasis-of-human-gastric-cancer-cells-sgc7901-and-mkn74-in%C3%A2-vitro-through-pten-activation-and-dephosphorylation-of-akt-and-fak
#13
Xue-Song Zhang, Yan-Hua Hu, Hong-Yu Gao, Xiu-Wen Lan, Ying-Wei Xue
Migration and invasion are both vital causes of mortality in patients with gastric cancer. Therefore, the inhibition of these tumour cell processes is of great importance in gastric cancer therapy. Activation of Notch has been reported in many cancers. The critical role of Notch and its regulation in tumourigenesis has been noted. Although the studies on Notch in the field of cancer have been performed extensively, the role of Notch1 signalling in gastric cancer requires further study. Inactivation of PTEN has been observed in the development of many malignant tumors, and loss of PTEN function has been implicated in tumorigenic processes...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626016/the-mtor-substrate-s6-kinase-1-s6k1-is-a-negative-regulator-of-axon-regeneration-and-a-potential-drug-target-for-central-nervous-system-injury
#14
Hassan Al-Ali, Ying Ding, Tatiana Slepak, Wei Wu, Yan Sun, Yania Martinez, Xiao-Ming Xu, V P Lemmon, J L Bixby
The mammalian target of Rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Though axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 Kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR's positive effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by 2-3 fold...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28623358/the-role-of-pten-hcv-core-interaction-in-hepatitis-c-virus-replication
#15
Qi Wu, Zhubing Li, Paul Mellor, Yan Zhou, Deborah H Anderson, Qiang Liu
Hepatitis C virus (HCV) infection leads to severe liver diseases including hepatocellular carcinoma (HCC). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumour suppressor, is frequently mutated or deleted in HCC tumors. PTEN has previously been demonstrated to inhibit HCV secretion. In this study, we determined the effects of PTEN on the other steps in HCV life cycle, including entry, translation, and replication. We showed that PTEN inhibits HCV entry through its lipid phosphatase activity...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623166/casein-kinase-ii-ck2-glycogen-synthase-kinase-3-gsk-3-and-ikaros-mediated-regulation-of-leukemia
#16
REVIEW
Chandrika Gowda, Mario Soliman, Malika Kapadia, Yali Ding, Kimberly Payne, Sinisa Dovat
Signaling networks that regulate cellular proliferation often involve complex interactions between several signaling pathways. In this manuscript we review the crosstalk between the Casein Kinase II (CK2) and Glycogen Synthase Kinase-3 (GSK-3) pathways that plays a critical role in the regulation of cellular proliferation in leukemia. Both CK2 and GSK-3 are potential targets for anti-leukemia treatment. Previously published data suggest that CK2 and GSK-3 act synergistically to promote the phosphatidylinositol-3 kinase (PI3K) pathway via phosphorylation of PTEN...
June 13, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28623072/commentary-on-integrative-clinical-genomics-of-advanced-prostate-cancer-robinson-d-van-allen-em-wu-ym-schultz-n-lonigro-rj-mosquera-jm-montgomery-b-taplin-me-pritchard-cc-attard-g-beltran-h-abida-w-bradley-rk-vinson-j-cao-x-vats-p-kunju-lp-hussain-m-feng-fy
#17
Stephen J Freedland, William J Aronson
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28622040/analysis-of-differential-genetic-expression-in-endometrial-polyps-of-postmenopausal-women
#18
J K Troncon, J Meola, F J Candido-Dos-Reis, O B Poli-Neto, A A Nogueira, J C Rosa-E-Silva
OBJECTIVES: To evaluate the expression of four genetic markers (PTEN, BCL2, MLH1, and CTNNB1), linked to endometrial carcinogenesis, in endometrial polyps of patients with and without postmenopausal bleeding in order to determine whether symptomatic endometrial polyps have a genetic phenotype similar to that of endometrial cancer. METHODS: Samples were obtained hysteroscopically from endometrial polyps of postmenopausal patients, and the expression of genetic markers involved in the pathogenesis of endometrial cancer (PTEN, BCL2, MLH1, and CTNNB1) was analyzed...
June 16, 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28621226/pten-a-potential-prognostic-marker-in-virus-induced-hepatocellular-carcinoma
#19
REVIEW
Ayesha Khalid, Tabinda Hussain, Sobia Manzoor, Muhammad Saalim, Saba Khaliq
PTEN is the second most frequently mutated tumor suppresser gene in cancers after p53. Genetic and epigenetic alterations in the PTEN gene and its regulatory regions have been reported in various studies. PTEN is a crucial downregulator of the pro-survival phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway and also suppresses insulin signaling. Failure to regulate these pathways leads to increase in cell proliferation and migration which in turn promotes tumorigenesis. PTEN underexpression is mediated by a variety of cytokines and stress kinases which seem to collectively induce the RAS/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28620835/twenty-years-since-the-discovery-of-the-parkin-gene
#20
REVIEW
Nobutaka Hattori, Yoshikuni Mizuno
Nearly 20 years have passed since we identified the causative gene for a familial Parkinson's disease, parkin (now known as PARK2), in 1998. PARK2 is the most common gene responsible for young-onset Parkinson's disease. It codes for the protein Parkin RBR E3 ubiquitin-protein ligase (PARK2), which directly links to the ubiquitin-proteasome as a ubiquitin ligase. PARK2 is involved in mitophagy, which is a type of autophagy, in collaboration with PTEN-induced putative kinase 1 (PINK1). The PINK1 gene (previously known as PARK6) is also a causative gene for young-onset Parkinson's disease...
June 15, 2017: Journal of Neural Transmission
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