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https://www.readbyqxmd.com/read/27907907/expression-analysis-and-clinical-significance-of-eif4e-vegf-c-e-cadherin-and-mmp-2-in-colorectal-adenocarcinoma
#1
Minna Gao, Xiong Zhang, Dan Li, Ping He, Wenguang Tian, Bo Zeng
The underlying mechanisms of colorectal carcinoma (CRC) metastasis remain to be elucidated. The aim of this study is to investigate clinical significance and the expression of eIF4E, VEGF-C, MMP-2, and E-cadherin in the CRC metastasis. We investigated their expressions in 108 patients, analyzed the relationships between their expressions in CRC and evaluated the relationships between their expressions and clinical pathogenic parameters. Furthermore, their roles in patient survival and in CRC metastasis were also investigated...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900644/elevated-levels-of-p-mnk1-p-eif4e-and-p-p70s6k-proteins-are-associated-with-tumor-recurrence-and-poor-prognosis-in-astrocytomas
#2
Weibing Fan, Weiyuan Wang, Xinfa Mao, Shuzhou Chu, Juan Feng, Desheng Xiao, Jianhua Zhou, Songqing Fan
Malignant astrocytomas are able to invade neighboring and distant areas of the normal brain. Signaling pathway alterations play important role in the development of astrocytomas. Deregulation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 directly or PI3K/mTOR/S6K pathway indirectly has a critical effect on promoting cellular proliferation, malignant transformation and metastasis. We examined and analyzed the correlation between expression of p-Mnk1, p-eIF4E and p-p70S6K proteins and clinicopathological features in 103 astrocytomas and 54 non-tumorous brain tissues...
November 29, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27899988/mtor-downstream-effectors-4ebp1-and-eif4e-are-overexpressed-and-associated-with-hpv-status-in-precancerous-lesions-and-carcinomas-of-the-uterine-cervix
#3
Aristidis Asimomytis, Maria Karanikou, Alexander Rodolakis, Anna Vaiopoulou, Paraskevi Tsetsa, George Creatsas, Theodoros Stefos, Aristidis Antsaklis, Efstratios Patsouris, George Z Rassidakis
The present study aims to investigate the expression levels of two critical mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous squamous intraepithelial lesions and cancer of the uterine cervix, and their association with human papilloma virus (HPV) infection status. Uterine cervical biopsies from 73 patients were obtained, including 40 fresh-frozen samples and 42 archival formalin-fixed, paraffin-embedded tissue specimens...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27879264/differential-regulation-of-the-melanoma-proteome-by-eif4a1-and-eif4e
#4
Cailin E Joyce, Adrienne G Yanez, Akihiro Mori, Akinori Yoda, Johanna S Carroll, Carl D Novina
Small molecules and antisense oligonucleotides that inhibit the translation initiation factors eIF4A1 and eIF4E have been explored as broad-based therapeutic agents for cancer treatment, based on the frequent upregulation of these two subunits of the eIF4F cap-binding complex in many cancer cells. Here we provide support for these therapeutic approaches with mechanistic studies of eIF4F-driven tumor progression in a preclinical model of melanoma. Silencing eIF4A1 or eIF4E decreases melanoma proliferation and invasion...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27871897/sauchinone-exerts-anticancer-effects-by-targeting-ampk-signaling-in-hepatocellular-carcinoma-cells
#5
Young Woo Kim, Eun Jeong Jang, Chang-Hyun Kim, Ju-Hee Lee
Sauchinone is a pharmacologically active compound isolated from Saururus chinensis, which has been used as a traditional Oriental medicine to treat fever, jaundice, and various inflammatory diseases. In this study, we investigated the effect of sauchinone against hepatocellular carcinoma (HCC) and sought to elucidate the mechanism involved. Cell viability was measured by an MTT assay. Cell cycle distributions and the mitochondrial membrane potential were analyzed using flow cytometry. Cell death was analyzed by annexin V assay, 4',6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay...
November 18, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27858515/eif4b-stimulates-eif4a-atpase-and-unwinding-activities-by-direct-interaction-through-its-7-repeats-region
#6
Alexandra Zoi Andreou, Ulf Harms, Dagmar Klostermeier
Eukaryotic translation initiation starts with binding of the eIF4F complex to the 5'-m7G cap of the mRNA. Recruitment of the 43S pre-initiation complex (PIC), formed by the 40S ribosomal subunit and other translation initiation factors, leads to formation of the 48S PIC that then scans the 5'-untranslated region (5'-UTR) towards the start codon. The eIF4F complex consists of eIF4E, the cap binding protein, eIF4A, a DEAD-box RNA helicase that is believed to unwind secondary structures in the 5'UTR during scanning, and eIF4G, a scaffold protein that binds to both eIF4E and eIF4A...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27836976/stress-granule-induction-after-brain-ischemia-is-independent-of-eukaryotic-translation-initiation-factor-eif-2%C3%AE-phosphorylation-and-is-correlated-with-a-decrease-in-eif4b-and-eif4e-proteins
#7
María Irene Ayuso, Emma Martínez-Alonso, Ignacio Regidor, Alberto Alcázar
Stress granules (SGs) are cytoplasmic ribonucleoprotein aggregates that are directly connected with the translation-initiation arrest response to cellular stresses. Translation inhibition (TI) is observed in transient brain ischemia, condition which induces persistent TI even after reperfusion, i.e., when blood flow is restored, and causes delayed neuronal death (DND) in selective vulnerable regions. We previously described a connection between TI and DND in the hippocampal cornu ammonis 1 (CA1) in an animal model of transient brain ischemia...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27833593/recessive-resistance-to-plant-viruses-potential-resistance-genes-beyond-translation-initiation-factors
#8
REVIEW
Masayoshi Hashimoto, Yutaro Neriya, Yasuyuki Yamaji, Shigetou Namba
The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant's resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27826040/dying-glioma-cells-establish-a-proangiogenic-microenvironment-through-a-caspase-3-dependent-mechanism
#9
Xiao Feng, Yang Yu, Sijia He, Jin Cheng, Yanping Gong, Zhengxiang Zhang, Xuguang Yang, Bing Xu, Xinjian Liu, Chuan-Yuan Li, Ling Tian, Qian Huang
Vascular recovery or re-angiogenesis after radiotherapy plays a significant role in tumor recurrence, whereas molecular mechanisms of this process remain elusive. In this work, we found that dying glioma cells promoted post-irradiation angiogenesis through a caspase 3 dependent mechanism. Evidence in vitro and in vivo indicated that caspase 3 inhibition undermined proangiogenic effects of dying glioma cells. Proteolytic inactivation of caspase 3 in glioma cells reduced tumorigenicity. Importantly, we identified that NF-κB/COX-2/PGE2 axis acted as downstream signaling of caspase 3, mediating proangiogenic response after irradiation...
November 5, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27825141/p73-expression-is-regulated-by-ribosomal-protein-rpl26-through-mrna-translation-and-protein-stability
#10
Min Zhang, Jin Zhang, Wensheng Yan, Xinbin Chen
p73, a p53 family tumor suppressor, is regulated by multiple mechanisms, including transcription and mRNA and protein stability. However, whether p73 expression is regulated via mRNA translation has not been explored. To test this, we examined whether ribosomal protein 26 (RPL26) plays a role in p73 expression. Here, we showed that p73 expression is controlled by RPL26 via protein stability and mRNA translation. To examine whether MDM2 mediates RPL26 to regulate p73 protein stability, we generated multiple MDM2-knockout cell lines by CRISPR-cas9...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27824302/new-insights-into-the-topology-of-the-scanning-ribosome-during-translation-initiation-lessons-from-viruses
#11
René Toribio, Irene Díaz-López, Iván Ventoso
Location of the translation initiation codon generally requires scanning of the 43S ribosomal preinitiation complex (43S PIC) from the 5' of the mRNA. Associated RNA helicases can facilitate movement of the 43S PIC by removing secondary structure present in the 5' UTR of mRNA, which is required for codon inspection. The canonical RNA-dependent helicase eIF4A is directly involved in this process, as part of the eIF4F complex (eIF4G+eIF4A+eIF4E) that associates first with mRNA and then recruits the 43S PIC to initiate scanning...
November 8, 2016: RNA Biology
https://www.readbyqxmd.com/read/27822137/axitinib-has-antiangiogenic-and-antitumorigenic-activity-in-myxoid-liposarcoma
#12
Lauren T Kerr, Jacqueline F Donoghue, Alexander L Wilding, Terrance G Johns
Myxoid liposarcoma is a rare form of soft-tissue sarcoma. Although most patients initially respond well to treatment, approximately 21% relapse, highlighting the need for alternative treatments. To identify novel treatment regimens and gain a better understanding of myxoid liposarcoma tumor biology, we screened various candidate and approved targeted therapeutics and chemotherapeutics against myxoid liposarcoma cell lines. Therapeutics that target angiogenesis showed antitumor activity. The small molecule inhibitor axitinib, which targets angiogenesis by inhibiting the VEGFR and PDGFR families and c-Kit, inhibited cell cycle progression and induced apoptosis in vitro, as well as having significant antitumor activity against MLS 1765 myxoid liposarcoma xenografts in mice...
2016: Sarcoma
https://www.readbyqxmd.com/read/27785922/inhibition-of-mnk-eif4e-pathway-sensitizes-the-efficacy-to-chemotherapy-in-anaplastic-thyroid-cancer
#13
Kun Hu, Juan Zhang, Min Yu, Chang'e Xiong
AIM: We investigated whether MAPK-interacting kinase (Mnk) inhibition sensitizes anaplastic thyroid cancer (ATC) cellular response to chemotherapy. MATERIALS & METHODS: In vitro and in vivo methods were used to examine the combinatory effects of cisplatin with Mnk inhibition and its underlying mechanism. RESULTS: Mnk inhibition by pharmacological or genetic approaches inhibits proliferation and induces apoptosis of ATC cells and enhances the effects of cisplatin in in vitro and in vivo...
October 27, 2016: Future Oncology
https://www.readbyqxmd.com/read/27784673/silencing-c-myc-translation-as-a-therapeutic-strategy-through-targeting-pi3k-delta-and-ck1-epsilon-in-hematological-malignancies
#14
Changchun Deng, Mark R Lipstein, Luigi Scotto, Xavier O Jirau Serrano, Michael A Mangone, Shirong Li, Jeremie Vendome, Yun Hao, Xiaoming Xu, Shi-Xian Deng, Ronald B Realubit, Nicholas P Tatonetti, Charles Karan, Suzanne Lentzsch, David A Fruman, Barry Honig, Donald W Landry, Owen A O'Connor
Phosphoinositide 3-kinase (PI3K) and the proteasome pathway are both involved in activating the mechanistic target of rapamycin (mTOR). Because mTOR signaling is required for initiation of mRNA translation, we hypothesized that co-targeting the PI3K and proteasome pathways might synergistically inhibit translation of c-Myc. We found that a novel PI3K delta isoform inhibitor TGR-1202, but not the approved PI3Kδ inhibitor idelalisib, was highly synergistic with the proteasome inhibitor carfilzomib in lymphoma, leukemia, and myeloma cell lines and primary lymphoma and leukemia cells...
October 26, 2016: Blood
https://www.readbyqxmd.com/read/27773676/the-structures-of-eif4e-eif4g-complexes-reveal-an-extended-interface-to-regulate-translation-initiation
#15
Stefan Grüner, Daniel Peter, Ramona Weber, Lara Wohlbold, Min-Yi Chung, Oliver Weichenrieder, Eugene Valkov, Cátia Igreja, Elisa Izaurralde
Eukaryotic initiation factor 4G (eIF4G) plays a central role in translation initiation through its interactions with the cap-binding protein eIF4E. This interaction is a major drug target for repressing translation and is naturally regulated by 4E-binding proteins (4E-BPs). 4E-BPs and eIF4G compete for binding to the eIF4E dorsal surface via a shared canonical 4E-binding motif, but also contain auxiliary eIF4E-binding sequences, which were assumed to contact non-overlapping eIF4E surfaces. However, it is unknown how metazoan eIF4G auxiliary sequences bind eIF4E...
October 19, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27763553/4ebp-dependent-signaling-supports-west-nile-virus-growth-and-protein-expression
#16
Katherine D Shives, Aaron R Massey, Nicholas A May, Thomas E Morrison, J David Beckham
West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an (m7)GpppNm 5' cap with 2'-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown...
October 18, 2016: Viruses
https://www.readbyqxmd.com/read/27760840/mtorc1-signalling-and-eif4e-4e-bp-1-translation-initiation-factor-stoichiometry-influence-recombinant-protein-productivity-from-gs-chok1-cells
#17
Lyne Jossé, Jianling Xie, Christopher Gregory Proud, C Mark Smales
Many protein-based biotherapeutics are produced in cultured Chinese hamster ovary (CHO) cell lines. Recent reports have demonstrated that translation of recombinant mRNAs and global control of the translation machinery via mammalian target of rapamycin (mTOR) signalling are important determinants of the amount and quality of recombinant protein such cells can produce. mTOR complex 1 (mTORC1) is a master regulator of cell growth/division, ribosome biogenesis and protein synthesis, but the relationship between mTORC1 signalling, cell growth and proliferation and recombinant protein yields from mammalian cells, and whether this master regulating signalling pathway can be manipulated to enhance cell biomass and recombinant protein production (rPP) are not well explored...
October 19, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27749759/restorative-mechanisms-regulating-protein-balance-in-skeletal-muscle-during-recovery-from-sepsis
#18
Kristen T Crowell, David I Soybel, Charles H Lang
Muscle deconditioning is commonly observed in patients surviving sepsis. Little is known regarding the molecular mechanisms regulating muscle protein homeostasis during the recovery or convalescence phase. We adapted a sepsis-recovery mouse model that uses cecal ligation and puncture (CLP), followed 24 h later by cecal resection and antibiotic treatment, to identify putative cellular pathways regulating protein synthesis and breakdown in skeletal muscle. Ten days after CLP, body weight and food consumption did not differ between control and sepsis-recovery mice, but gastrocnemius weight was reduced...
October 5, 2016: Shock
https://www.readbyqxmd.com/read/27748944/hpip-promotes-gastric-cancer-cell-proliferation-through-activation-of-cap-dependent-translation
#19
Bing Chen, Jin Zhao, Shengbin Zhang, Yonggang Zhang, Zonghai Huang
Cap-dependent translation has an essential role in the control of cell proliferation by initiating the translation of oncogenes involved in the regulation of cell cycle progression, such as cyclin D1, and its deregulation contributes to the development and progression of various types of cancers. Hematopoietic pre-B-cell leukemia transcription factor interacting protein (HPIP) was found to be overexpressed in gastric cancer (GC) tissues compared to normal tissues and to promote GC growth in vitro and in vivo...
October 11, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27746794/barley-yellow-mosaic-virus-vpg-is-the-determinant-protein-for-breaking-eif4e-mediated-recessive-resistance-in-barley-plants
#20
Huangai Li, Hideki Kondo, Thomas Kühne, Yukio Shirako
In this study, we investigated the barley yellow mosaic virus (BaYMV, genus Bymovirus) factor(s) responsible for breaking eIF4E-mediated recessive resistance genes (rym4/5/6) in barley. Genome mapping analysis using chimeric infectious cDNA clones between rym5-breaking (JT10) and rym5-non-breaking (JK05) isolates indicated that genome-linked viral protein (VPg) is the determinant protein for breaking the rym5 resistance. Likewise, VPg is also responsible for overcoming the resistances of rym4 and rym6 alleles...
2016: Frontiers in Plant Science
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