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https://www.readbyqxmd.com/read/28933585/oncogenic-ras-induced-downregulation-of-atg12-is-required-for-survival-of-malignant-intestinal-epithelial-cells
#1
Byong Hoon Yoo, Iman Aftab Khan, Ananda Koomson, Pramod Gowda, Takehiko Sasazuki, Senji Shirasawa, Shashi Gujar, Kirill Rosen
Activating mutations of RAS GTPase contribute to the progression of many cancers, including colorectal carcinoma. So far, attempts to develop treatments of mutant RAS-carrying cancers have been unsuccessful owing to insufficient understanding of the salient mechanisms of RAS signalling. We found that RAS downregulates the protein ATG12 in colon cancer cells. ATG12 is a mediator of autophagy, a process of degradation and reutilization of cellular components. In addition, ATG12 can kill cells via autophagy-independent mechanisms...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933561/ckap2-promotes-ovarian-cancer-proliferation-and-tumorigenesis-through-the-fak-erk-pathway
#2
Mei Zhang, Longjun Zhao
Upregulation of cytoskeleton-associated protein 2 (CKAP2) has been observed in ovarian cancer. This study aimed to determine the effects of overexpression of CKAP2 on cell proliferation and tumorigenesis and to explore the potential signal pathway in the oncogenic process. Expression of CKAP2 in tissue of ovarian cancer patients was detected. Human cancer cell line SKOV3 was overexpressed with CKAP2 and measured for cell growth and mobility. Moreover, CKAP2 effect was estimated using mouse tumor xenografts...
September 21, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28922853/a-rationale-for-targeting-extracellular-regulated-kinases-erk1-and-erk2-in-glioblastoma
#3
Ricarda Hannen, Maria Hauswald, Joerg Walter Bartsch
Glioblastoma (GBM) is the most common malignant primary brain tumor. It still carries a grim prognosis and new therapies are needed. This review summarizes the current status of mechanistic insights into the function of extracellular regulated kinase (ERK) and its potential as a therapeutic target for patients with GBM. Currently, some promising ERK inhibitors are in clinical trials in tumor entities other than GBM. Here, we provide a comprehensive overview on the functions of ERK1/2 in GBM and a rationale for treatment of GBM with ERK inhibitors...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28915648/synergistic-suppression-of-t-8-21-positive-leukemia-cell-growth-by-combining-oridonin-and-mapk1-erk2-inhibitors
#4
Pavel Spirin, Timofey Lebedev, Natalia Orlova, Alexey Morozov, Nadezhda Poymenova, Sergey E Dmitriev, Anton Buzdin, Carol Stocking, Olga Kovalchuk, Vladimir Prassolov
One of the most common chromosomal translocations in acute myeloid leukemia is t(8;21)(q22;q22), which results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO. Therefore, this oncoprotein is considered to be a pertinent and promising target for treating t(8;21) leukemia. Previously, we have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell survival and determined that the protein ERK2 can mediate activation of most of these pathways...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28861806/rutaecarpine-inhibits-intimal-hyperplasia-in-a-balloon-injured-rat-artery-model
#5
Yang Xu, Xiu-Ping Chen, Feng Zhang, Hua-Hua Hou, Jing-Yi Zhang, Shu-Xian Lin, An-Sheng Sun
OBJECTIVE: To investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model. METHODS: The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into fifive groups, ie. sham, model, Rut (25, 50 and 75 mg/kg) with 10 rats of each group. The rats were treated with or without Rut (25, 50, 75 mg/kg) by intragastric administration for 14 consecutive days following injury...
September 1, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28844099/epigenetic-silencing-of-prss3-provides-growth-and-metastasis-advantage-for-human-hepatocellular-carcinoma
#6
Bonan Lin, Xiaomeng Zhou, Shuye Lin, Xiaoyue Wang, Meiying Zhang, Baoping Cao, Yan Dong, Shuai Yang, Ji Ming Wang, Mingzhou Guo, Jiaqiang Huang
Protease, serine, 3 (PRSS3), a member of the trypsin family of serine proteases, has been shown to be aberrantly expressed in several cancer types and to play important roles in tumor progression and metastasis. However, the expression and function of PRSS3 gene in hepatocellular carcinoma (HCC) remain unclear. Here we found that PRSS3 expression was decreased in human HCC cell lines and HCC surgical specimens. This was associated with intragenic methylation of PRSS3 gene. Treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor trichostatin A restored PRSS3 expression in HCC cell lines...
August 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28833860/chronic-impairment-of-erk-signaling-in-glutamatergic-neurons-of-the-forebrain-does-not-affect-spatial-memory-retention-and-ltp-in-the-same-manner-as-acute-blockade-of-the-erk-pathway
#7
Joseph Vithayathil, Joanna Pucilowska, David Friel, Gary E Landreth
The ERK/MAPK signaling pathway has been extensively studied in the context of learning and memory. Defects in this pathway underlie genetic diseases associated with intellectual disability, including impaired learning and memory. Numerous studies have investigated the impact of acute ERK/MAPK inhibition on long-term potentiation and spatial memory. However, genetic knockouts of the ERKs have not been utilized to determine whether developmental perturbations of ERK/MAPK signaling affect LTP and memory formation in postnatal life...
August 17, 2017: Hippocampus
https://www.readbyqxmd.com/read/28806729/erk2-and-jnk1-contribute-to-tnf-%C3%AE-induced-il-8-expression-in-synovial-fibroblasts
#8
Shinichi Namba, Rei Nakano, Taku Kitanaka, Nanako Kitanaka, Tomohiro Nakayama, Hiroshi Sugiya
Tumor necrosis factor α (TNF-α) induces the expression and secretion of interleukin 8 (IL-8), which contributes to synovitis in rheumatoid arthritis (RA). To elucidate the mechanism of the onset of RA, we used synovial fibroblasts without autoimmune inflammatory diseases and investigated MAPK signaling pathways in TNF-α-induced IL-8 expression. Synovial fibroblasts isolated from healthy dogs were characterized by flow cytometry, which were positive for the fibroblast markers CD29, CD44, and CD90 but negative for the hematopoietic cell markers CD14, CD34, CD45, and HLA-DR...
2017: PloS One
https://www.readbyqxmd.com/read/28769771/upregulation-of-matrix-metalloproteinase-9-in-primary-cultured-rat-astrocytes-induced-by-2-chloroethanol-via-mapk-signal-pathways
#9
Tong Wang, Yingjun Liao, Qi Sun, Hongge Tang, Gaoyang Wang, Fenghong Zhao, Yaping Jin
2-Chloroethanol (2-CE) is one of the reactive metabolites of 1,2-DCE in vivo, which might contribute to brain edema formation induced by 1,2-dichloroethane (1,2-DCE) poisoning. Thus, the purpose of this study was to explore the roles of mitogen-activated protein kinase (MAPK) signal pathways in upregulation of matrix metalloproteinase-9 (MMP-9) in 2-CE exposed rat astrocytes. Expression of p38 MAPK (p38), extracellular signal regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and MMP-9 at both protein and gene levels in rat astrocytes were determined using western blot and real-time RT-PCR methods...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28739735/knockdown-of-epha1-using-crispr-cas9-suppresses-aggressive-properties-of-ovarian-cancer-cells
#10
Yuxin Cui, B O Wu, Valentina Flamini, Bronwen A J Evans, Deshan Zhou, Wen G Jiang
BACKGROUND/AIM: Overexpression of erythropoietin-producing hepatocellular A1 (EPHA1), a member of the EPH super family, is frequently observed in various cancer types. The dysregulated interaction of EPHA1 with its ligand Ephrin A1 has been linked to the progression of ovarian cancer (OC). However, the contribution of EPHA1 in the regulation of the aggressive properties of OC cells remains unknown. MATERIALS AND METHODS: In this study we investigated the differential expression of EPHA1 in human OC cells...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28736134/stimulus-evoked-erk-dependent-phosphorylation-of-activity-regulated-cytoskeleton-associated-protein-arc-regulates-its-neuronal-subcellular-localization
#11
Oleksii Nikolaienko, Maria Steene Eriksen, Sudarshan Patil, Haruhiko Bito, Clive R Bramham
Activity-regulated cytoskeletal-associated protein (Arc) is implicated as a master regulator of long-term synaptic plasticity and memory formation in mammalian brain. Arc acts at synapses and within the nucleus, but the mechanisms controlling Arc localization and function are little known. As Arc transcription and translation are regulated by extracellularsignal-regulated kinase (ERK) signaling, we asked whether Arc protein itself is phosphorylated by ERK. GST-fused Arc of rat origin was able to pull down endogenous ERK2 from rat hippocampal lysates...
July 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28721437/erk1-is-dispensable-for-mouse-pancreatic-beta-cell-function-but-is-necessary-for-glucose-induced-full-activation-of-msk1-and-creb
#12
Michele Leduc, Joy Richard, Safia Costes, Dany Muller, Annie Varrault, Vincent Compan, Julia Mathieu, Jean-François Tanti, Gilles Pagès, Jacques Pouyssegur, Gyslaine Bertrand, Stéphane Dalle, Magalie A Ravier
AIMS/HYPOTHESIS: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 (-/-) mice) and pharmacological approaches...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28716922/local-destabilization-rigid-body-and-fuzzy-docking-facilitate-the-phosphorylation-of-the-transcription-factor-ets-1-by-the-mitogen-activated-protein-kinase-erk2
#13
Andrea Piserchio, Mangalika Warthaka, Tamer S Kaoud, Kari Callaway, Kevin N Dalby, Ranajeet Ghose
Mitogen-activated protein (MAP) kinase substrates are believed to require consensus docking motifs (D-site, F-site) to engage and facilitate efficient site-specific phosphorylation at specific serine/threonine-proline sequences by their cognate kinases. In contrast to other MAP kinase substrates, the transcription factor Ets-1 has no canonical docking motifs, yet it is efficiently phosphorylated by the MAP kinase ERK2 at a consensus threonine site (T38). Using NMR methodology, we demonstrate that this phosphorylation is enabled by a unique bipartite mode of ERK2 engagement by Ets-1 and involves two suboptimal noncanonical docking interactions instead of a single canonical docking motif...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28689659/bcl3-phosphorylation-by-akt-erk2-and-ikk-is-required-for-its-transcriptional-activity
#14
Vivien Ya-Fan Wang, Yidan Li, Daniel Kim, Xiangyang Zhong, Qian Du, Majid Ghassemian, Gourisankar Ghosh
Unlike prototypical IκB proteins, which are inhibitors of NF-κB RelA, cRel, and RelB dimers, the atypical IκB protein Bcl3 is primarily a transcriptional coregulator of p52 and p50 homodimers. Bcl3 exists as phospho-protein in many cancer cells. Unphosphorylated Bcl3 acts as a classical IκB-like inhibitor and removes p50 and p52 from bound DNA. Neither the phosphorylation site(s) nor the kinase(s) phosphorylating Bcl3 is known. Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28665544/pioglitazone-attenuates-atrial-remodeling-and-vulnerability-to-atrial-fibrillation-in-alloxan-induced-diabetic-rabbits
#15
Changle Liu, Ruimeng Liu, Huaying Fu, Jian Li, Xinghua Wang, Lijun Cheng, Panagiotis Korantzopoulos, Gary Tse, Guangping Li, Tong Liu
BACKGROUND/AIMS: Recent evidence indicates that peroxisome proliferator-activated receptor (PPAR)-γ activators exert anti-inflammatory and anti-oxidant actions. However, the underlying mechanisms by which these agents prevent atrial remodeling in diabetes are not completely elucidated. We sought to investigate the potential effects of pioglitazone, a PPAR-γ activator, on atrial remodeling and atrial fibrillation (AF) inducibility in diabetic rabbits. METHODS: Alloxan-induced diabetic rabbits were randomly divided into three groups: diabetes only, diabetes treated with low-dose pioglitazone (4 mg/day/kg), or diabetes treated with high dose pioglitazone (8 mg/day/kg) (n = 24 for each group)...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28662520/regulation-of-ap-1-by-mapk-signaling-in-metal-stressed-sea-anemone
#16
Maayan Agron, Vera Brekhman, David Morgenstern, Tamar Lotan
BACKGROUND/AIMS: AP-1 transcription factor plays a conserved role in the immediate response to stress. Activation of AP-1 members jun and fos is mediated by complex signaling cascades to control cell proliferation and survival. To understand the evolution of this broadly-shared pathway, we studied AP-1 regulation by MAPK signaling in a basal metazoan. METHODS: Metal- stressed cnidarian Nematostella vectensis anemones were tested with kinase inhibitors and analyzed for gene expression levels and protein phosphorylation...
June 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28656208/effect-of-nonylphenol-on-the-regulation-of-cell-growth-in-colorectal-cancer-cells
#17
Xuefeng Yang, Handong Huang, Maijian Wang, Xingbin Zheng, Jie Xu, Ming Xie
Nonylphenol (NP) is a well-known endocrine-disrupting chemical (EDC), which can enhance the progression of cancer by functioning as an estrogen‑like factor. In the present study, the effects of different concentrations of NP on COLO205 colorectal cancer (CRC) cells were examined. The results of flow cytometric analysis revealed that NP significantly decreased the proportion of cells in the G0/G1 phase in a dose‑dependent manner, which was accompanied by a marginal increase in the proportions of cells in S and G2/M phases...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28654903/synergistic-suppression-of-t-8-21-positive-leukemia-cell-growth-by-combining-oridonin-and-mapk1-erk2-inhibitors
#18
Pavel Spirin, Timofey Lebedev, Natalia Orlova, Alexey Morozov, Nadezhda Poymenova, Sergey E Dmitriev, Anton Buzdin, Carol Stocking, Kovalchuk Olga, Prassolov Vladimir
One of the most common chromosomal translocations in acute myeloid leukemia is t(8;21)(q22;q22), which results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO. Therefore, this oncoprotein is considered to be a pertinent and promising target for treating t(8;21) leukemia. Previously, we have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell survival and determined that the protein ERK2 can mediate activation of most of these pathways...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28638727/identification-of-an-immunogenic-neo-epitope-encoded-by-mouse-sarcoma-using-cxcr3-ligand-mrnas-as-sensors
#19
Keisuke Fujii, Yoshihiro Miyahara, Naozumi Harada, Daisuke Muraoka, Mitsuhiro Komura, Rui Yamaguchi, Hideo Yagita, Junko Nakamura, Sahoko Sugino, Satoshi Okumura, Seiya Imoto, Satoru Miyano, Hiroshi Shiku
The CXCR3 ligands CXCL9, 10, and 11 play critical roles in the amplification of immune responses by recruiting CXCR3(+) immune effector cells to the tumor site. Taking advantage of this property of CXCR3 ligands, we aimed to establish a novel approach to identify immunogenic mutated-antigens. We examined the feasibility of using CXCR3 ligand mRNAs as sensors for detection of specific immune responses in human and murine systems. We further investigated whether this approach is applicable for the identification of immunogenic mutated-antigens by using murine sarcoma lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28623314/comparative-transcriptomic-and-proteomic-analyses-provide-insights-into-the-key-genes-involved-in-high-altitude-adaptation-in-the-tibetan-pig
#20
Bo Zhang, Yangzom Chamba, Peng Shang, Zhixiu Wang, Jun Ma, Liyuang Wang, Hao Zhang
Tibetan pigs that inhabit the Tibetan Plateau exhibit striking phenotypic and physiological differences from lowland pigs, and have adapted well to extreme conditions. However, the mechanisms involved in regulating gene expression at high altitude in these animals are not fully understood. In this study, we obtained transcriptomic and proteomic data from the heart tissues of Tibetan and Yorkshire pigs raised in the highlands (TH and YH) and lowlands (TL and YL) via RNA-seq and iTRAQ (isobaric tags for relative and absolute quantitation) analyses, respectively...
June 16, 2017: Scientific Reports
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