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https://www.readbyqxmd.com/read/29098032/identification-of-mirna-and-genes-involving-in-osteosarcoma-by-comprehensive-analysis-of-microrna-and-copy-number-variation-data
#1
Tao Luo, Xiangli Yi, Wei Si
The aim of the present study was to understand the molecular mechanisms of osteosarcoma by comprehensive analysis of microRNA (miRNA/miR) and copy number variation (CNV) microarray data. Microarray data (GSE65071 and GSE33153) were downloaded from the Gene Expression Omnibus. In GSE65071, differentially expressed miRNAs between the osteosarcoma and control groups were calculated by the Limma package. Target genes of differentially expressed miRNAs were identified by the starBase database. For GSE33153, PennCNV software was used to perform the copy number variation (CNV) analysis...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/28947594/mir-339-inhibits-proliferation-of-pulmonary-artery-smooth-muscle-cell-by-targeting-fgf-signaling
#2
Jidong Chen, Xiaolei Cui, Li Li, Junle Qu, J Usha Raj, Deming Gou
Pulmonary artery hypertension (PAH) is a fatal disorder. Recent studies suggest that microRNA (miRNA) plays an important role in regulating proliferation of pulmonary artery smooth muscle cells (PASMC), which underlies the pathology of PAH However, the exact mechanism of action of miRNAs remains elusive. In this study, we found that miR-339 was highly expressed in the cardiovascular system and was downregulated by a group of cytokines and growth factors, especially PDGF-BB and FGF2. Functional analyses revealed that miR-339 can inhibit proliferation of PASMC Also, miR-339 inhibited FGF2-induced proliferation, but had no effect on proliferation induced by PDGF-BB The fibroblast growth factor receptor substrate 2 (FRS2) was identified as a potential direct target of miR-339...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28895643/thyroid-hormone-induced-expression-of-the-hepatic-scaffold-proteins-sestrin2-%C3%AE-klotho-and-frs2%C3%AE-in-relation-to-fgf21-ampk-signaling
#3
Luis A Videla, Romina Vargas, Barbara Riquelme, Javier Fernández, Virginia Fernández
Thyroid hormone (3,3',5-triiodothyronine, T3) accelerates energy metabolism in the liver through mechanisms involving upregulation of AMP-activated protein kinase (AMPK). This study aims to assess the influence of T3 on the expression of the scaffold proteins β-Klotho, fibroblast growth factor receptor substrate 2α (FRS2α), and Sestrin2 in relation to FGF21-AMPK signaling. Male Sprague-Dawley rats were given 0.1 mg T3/kg or hormone vehicle (controls) and studies were done 24 h after treatment. These include measurements of the mRNA expression (qPCR) of hepatic β-Klotho, FGF21, FGF21 receptor-1 (FGFR1), extracellular-signal-regulated kinase 1/2 (ERK1/2), FRS2α, ribosomal S6 kinase-1 (RSK1), liver kinase B1 (LKB1), AMPK, and Sestrin2...
September 11, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28829507/microrna-613-attenuates-the-proliferation-migration-and-invasion-of-wilms-tumor-via-targeting-frs2
#4
H-F Wang, Y-Y Zhang, H-W Zhuang, M Xu
OBJECTIVE: Wilms' tumor is the most common malignant tumor in children worldwide. Considering the poor therapeutic effect on Wilms' tumor, we determined the effects of microRNA-613 on cell proliferation and metastasis in vitro, providing therapeutic targets for the treatment of Wilms' tumor. PATIENTS AND METHODS: Quantitative real-time PCR (qRT-PCR) was employed to identify the expression level of miR-613. CCK8 and colony formation assays were incorporated to assess cell viability and proliferation capacity...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28771231/fgfr1-is-critical-for-the-anti-endothelial-mesenchymal-transition-effect-of-n-acetyl-seryl-aspartyl-lysyl-proline-via-induction-of-the-map4k4-pathway
#5
Jinpeng Li, Sen Shi, Swayam Prakash Srivastava, Munehiro Kitada, Takako Nagai, Kyoko Nitta, Miyuki Kohno, Keizo Kanasaki, Daisuke Koya
Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis, and we have reported that the anti-EndMT effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is associated with restoring expression of diabetes-suppressed fibroblast growth factor receptor (FGFR), the key anti-EndMT molecule. FGFR1 is the key inhibitor of EndMT via the suppression of the transforming growth factor β (TGFβ) signaling pathway, and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibits integrin β1, a key factor in activating TGFβ signaling and EndMT...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28558797/expression-of-signaling-adaptor-proteins-predicts-poor-prognosis-in-pancreatic-ductal-adenocarcinoma
#6
Lili Wang, Junliang Lu, Huanwen Wu, Li Wang, Xiaolong Liang, Zhiyong Liang, Tonghua Liu
BACKGROUND: Adaptor proteins bridge the gap between cell surface receptors and their downstream signaling elements. The clinicopathological and prognostic values of adaptor proteins remain poorly understood. The purpose of the present study was to explore the expression and prognostic value of three adaptor proteins: GRB2-associated binding protein 2 (GAB2), CRK-like protein (CRKL) and fibroblast growth factor receptor substrate 2 (FRS2) in pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of GAB2, CRKL, and FRS2 in 77 formalin fixed paraffin embedded (FFPE) samples from 77 PDAC patients, along with three paired fresh PDAC and matched normal tissues from 3 PDAC patients was analyzed by immunohistochemistry and western blot, respectively...
May 30, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28483978/fgf-dependent-context-driven-role-for-frs-adapters-in-the-early-telencephalon
#7
Sayan Nandi, Grigoriy Gutin, Christopher A Blackwood, Nachiket G Kamatkar, Kyung W Lee, Gordon Fishell, Fen Wang, Mitchell Goldfarb, Jean M Hébert
FGF signaling, an important component of intercellular communication, is required in many tissues throughout development to promote diverse cellular processes. Whether FGF receptors (FGFRs) accomplish such varied tasks in part by activating different intracellular transducers in different contexts remains unclear. Here, we used the developing mouse telencephalon as an example to study the role of the FRS adapters FRS2 and FRS3 in mediating the functions of FGFRs. Using tissue-specific and germline mutants, we examined the requirement of Frs genes in two FGFR-dependent processes...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28473845/pancreatic-islet-protein-complexes-and-their-dysregulation-in-type-2-diabetes
#8
Helle Krogh Pedersen, Valborg Gudmundsdottir, Søren Brunak
Type 2 diabetes (T2D) is a complex disease that involves multiple genes. Numerous risk loci have already been associated with T2D, although many susceptibility genes remain to be identified given heritability estimates. Systems biology approaches hold potential for discovering novel T2D genes by considering their biological context, such as tissue-specific protein interaction partners. Pancreatic islets are a key T2D tissue and many of the known genetic risk variants lead to impaired islet function, hence a better understanding of the islet-specific dysregulation in the disease-state is essential to unveil the full potential of person-specific profiles...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28445992/interaction-between-the-estrogen-receptor-and-fibroblast-growth-factor-receptor-pathways-in-non-small-cell-lung-cancer
#9
Jill M Siegfried, Mariya Farooqui, Natalie J Rothenberger, Sanja Dacic, Laura P Stabile
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424409/clinical-genomic-profiling-to-identify-actionable-alterations-for-investigational-therapies-in-patients-with-diverse-sarcomas
#10
Roman Groisberg, David S Hong, Vijaykumar Holla, Filip Janku, Sarina Piha-Paul, Vinod Ravi, Robert Benjamin, Shreyas Kumar Patel, Neeta Somaiah, Anthony Conley, Siraj M Ali, Alexa B Schrock, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Shiraj Sen, Cynthia Herzog, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: There are currently no United States Food and Drug Administration approved molecularly matched therapies for sarcomas except gastrointestinal stromal tumors. Complicating this is the extreme diversity, heterogeneity, and rarity of these neoplasms. Few therapeutic options exist for relapsed and refractory sarcomas. In clinical practice many oncologists refer patients for genomic profiling hoping for guidance on treatment options after standard therapy. However, a systematic analysis of actionable mutations has yet to be completed...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077787/androgen-suppresses-protein-kinase-d1-expression-through-fibroblast-growth-factor-receptor-substrate-2-in-prostate-cancer-cells
#11
Liyong Zhang, Zhenlong Zhao, Shuping Xu, Manuj Tandon, Courtney R LaValle, Fan Deng, Q Jane Wang
In prostate cancer, androgen/androgen receptor (AR) and their downstream targets play key roles in all stages of disease progression. The protein kinase D (PKD) family, particularly PKD1, has been implicated in prostate cancer biology. Here, we examined the cross-regulation of PKD1 by androgen signaling in prostate cancer cells. Our data showed that the transcription of PKD1 was repressed by androgen in androgen-sensitive prostate cancer cells. Steroid depletion caused up regulation of PKD1 transcript and protein, an effect that was reversed by the AR agonist R1881 in a time- and concentration-dependent manner, thus identifying PKD1 as a novel androgen-repressed gene...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27811184/coupling-an-eml4-alk-centric-interactome-with-rna-interference-identifies-sensitizers-to-alk-inhibitors
#12
Guolin Zhang, Hannah Scarborough, Jihye Kim, Andrii I Rozhok, Yian Ann Chen, Xiaohui Zhang, Lanxi Song, Yun Bai, Bin Fang, Richard Z Liu, John Koomen, Aik Choon Tan, James Degregori, Eric B Haura
Patients with lung cancers harboring anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment with ALK inhibitors, but acquired resistance inevitably arises. A better understanding of proximal ALK signaling mechanisms may identify sensitizers to ALK inhibitors that disrupt the balance between prosurvival and proapoptotic effector signals. Using affinity purification coupled with mass spectrometry in an ALK fusion lung cancer cell line (H3122), we generated an ALK signaling network and investigated signaling activity using tyrosine phosphoproteomics...
October 18, 2016: Science Signaling
https://www.readbyqxmd.com/read/27664399/in-silico-prediction-and-in-vitro-and-in-vivo-validation-of-acaricide-fluazuron-as-a-potential-inhibitor-of-fgfr3-and-a-candidate-anticancer-drug-for-bladder-carcinoma
#13
Kunbin Ke, Hongjian Li, Hong Yao, Xi-Nan Shi, Chao Dong, Ying Zhu, Xu Liu, Ling Li, Kwong-Sak Leung, Man-Hon Wong, Xiao-Dong Liu, Hsiang-Fu Kung, Marie Chia-Mi Lin
Bladder carcinoma (BC) is the ninth most common cause of cancer worldwide. Surgical resection and conventional chemotherapy and radiotherapy will ultimately fail due to tumor recurrence and resistance. Thus, the development of novel treatment is urgently needed. Fibroblast growth factor receptor 3 (FGFR3) is an important and well-established target for BC treatment. In this study, we utilized the free and open-source protein-ligand docking software idock to prospectively identify potential inhibitors of FGFR3 from 3,167 worldwide approved small-molecule drugs using a repositioning strategy...
April 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27615514/proximity-labeling-reveals-molecular-determinants-of-fgfr4-endosomal-transport
#14
Ellen Margrethe Haugsten, Vigdis Sørensen, Michaela Kunova Bosakova, Gustavo Antonio de Souza, Pavel Krejci, Antoni Wiedlocha, Jørgen Wesche
The fibroblast growth factor receptors (FGFRs) are important oncogenes promoting tumor progression in many types of cancer, such as breast, bladder, and lung cancer as well as multiple myeloma and rhabdomyosarcoma. However, little is known about how these receptors are internalized and down-regulated in cells. We have here applied proximity biotin labeling to identify proteins involved in FGFR4 signaling and trafficking. For this purpose we fused a mutated biotin ligase, BirA*, to the C-terminal tail of FGFR4 (FGFR4-BirA*) and the fusion protein was stably expressed in U2OS cells...
October 7, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27550940/identification-of-pharmacodynamic-transcript-biomarkers-in-response-to-fgfr-inhibition-by-azd4547
#15
Oona Delpuech, Claire Rooney, Lorraine Mooney, Dawn Baker, Robert Shaw, Michael Dymond, Dennis Wang, Pei Zhang, Sarah Cross, Margaret Veldman-Jones, Joanne Wilson, Barry R Davies, Jonathan R Dry, Elaine Kilgour, Paul D Smith
The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signaling inhibition by AZD4547, a potent inhibitor of FGF receptors 1, 2, and 3, a gene expression profiling study was performed in FGFR2-amplified, drug-sensitive tumor cell lines...
November 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27533459/mir-4653-3p-and-its-target-gene-frs2-are-prognostic-biomarkers-for-hormone-receptor-positive-breast-cancer-patients-receiving-tamoxifen-as-adjuvant-endocrine-therapy
#16
XiaoRong Zhong, GuiQin Xie, Zhang Zhang, Zhu Wang, Yu Wang, YanPing Wang, Yan Qiu, Li Li, Hong Bu, JiaYuan Li, Hong Zheng
Long-term tamoxifen treatment significantly improves the survival of hormone receptor-positive (HR+) breast cancer (BC) patients. However, tamoxifen resistance remains a challenge. We aimed to identify prognostic biomarkers for tamoxifen resistance and reveal the underlying mechanism. From March 2001 to September 2013, 400 HR+ BC women (stage I~III) were treated with adjuvant tamoxifen for 5 years or until relapse in West China Hospital. We included a discovery set of 6 patients who were refractory to tamoxifen, and a validation cohort of 88 patients including 35 cases with relapse...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27503856/unravelling-the-mechanism-of-trka-induced-cell-death-by-macropinocytosis-in-medulloblastoma-daoy-cells
#17
Chunhui Li, James I S MacDonald, Asghar Talebian, Jennifer Leuenberger, Claudia Seah, Stephen H Pasternak, Stephen W Michnick, Susan O Meakin
Macropinocytosis is a normal cellular process by which cells internalize extracellular fluids and nutrients from their environment and is one strategy that Ras-transformed pancreatic cancer cells use to increase uptake of amino acids to meet the needs of rapid growth. Paradoxically, in non-Ras transformed medulloblastoma brain tumors, we have shown that expression and activation of the receptor tyrosine kinase TrkA overactivates macropinocytosis, resulting in the catastrophic disintegration of the cell membrane and in tumor cell death...
October 15, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27409346/preclinical-evaluation-of-potential-therapeutic-targets-in-dedifferentiated-liposarcoma
#18
Robert Hanes, Iwona Grad, Susanne Lorenz, Eva W Stratford, Else Munthe, Chilamakuri Chandra Sekhar Reddy, Leonardo A Meza-Zepeda, Ola Myklebost
Sarcomas are rare cancers with limited treatment options. Patients are generally treated by chemotherapy and/or radiotherapy in combination with surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization of patient tumors to identify targetable mutations with in vitro testing of specific drugs in patient-derived cell lines. We have analyzed three metastases from a patient with high-grade metastatic dedifferentiated liposarcoma (DDLPS) by exome and transcriptome sequencing as well as DNA copy number analysis...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27392325/key-roles-of-emt-for-adaptive-resistance-to-mek-inhibitor-in-kras-mutant-lung-cancer
#19
Hidenori Kitai, Hiromichi Ebi
KRAS is frequently mutated in a variety of cancers including lung cancer. Whereas the mitogen-activated protein kinase (MAPK) is a well-known effector pathway of KRAS, blocking this pathway with MEK inhibitors is relatively ineffective. One major contributor to limited efficacy is attributed to the reactivation of MAPK signal following MEK inhibition by multiple feedback mechanisms. In a recent study, we have identified that epithelial-to-mesenchymal transition defines feedback activation of receptor tyrosine kinase signaling following MEK inhibition in KRAS mutant lung cancer...
July 3, 2017: Small GTPases
https://www.readbyqxmd.com/read/27338794/a-combinatorial-strategy-for-treating-kras-mutant-lung-cancer
#20
Eusebio Manchado, Susann Weissmueller, John P Morris, Chi-Chao Chen, Ramona Wullenkord, Amaia Lujambio, Elisa de Stanchina, John T Poirier, Justin F Gainor, Ryan B Corcoran, Jeffrey A Engelman, Charles M Rudin, Neal Rosen, Scott W Lowe
Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proved difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as single agents. Here we take a systematic approach towards identifying combination targets for trametinib, a MEK inhibitor approved by the US Food and Drug Administration, which acts downstream of KRAS to suppress signalling through the mitogen-activated protein kinase (MAPK) cascade...
June 30, 2016: Nature
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