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https://www.readbyqxmd.com/read/28332555/loxl2-drives-epithelial-mesenchymal-transition-via-activation-of-ire1-xbp1-signalling-pathway
#1
Eva P Cuevas, Pilar Eraso, María J Mazón, Vanesa Santos, Gema Moreno-Bueno, Amparo Cano, Francisco Portillo
Epithelial-to-Mesenchymal Transition (EMT) is a key process contributing to the aggressiveness of cancer cells. EMT is triggered by activation of different transcription factors collectively known as EMT-TFs. Different cellular cues and cell signalling networks activate EMT at transcriptional and posttranscriptional level in different biological and pathological situations. Among them, overexpression of LOXL2 (lysyl oxidase-like 2) induces EMT independent of its catalytic activity. Remarkably, perinuclear/cytoplasmic accumulation of LOXL2 is a poor prognosis marker of squamous cell carcinomas and is associated to basal breast cancer metastasis by mechanisms no yet fully understood...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#2
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene (Ensembl ID: ENSG00000044574 (WTSI/EMBL-EBI, 2015)) encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca(2+) homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28279065/proteomic-biomarkers-for-bisphenol-a-early-exposure-and-women-s-thyroid-cancer
#3
Ho-Sun Lee, Yunkyeong Kang, Kyung Tae, Gyu-Un Bae, Jong Y Park, Yoon Hee Cho, Mihi Yang
Purpose: For the target treatment and prevention of women's increased thyroid cancer, we focused on risks of environmental exposure to endocrine disrupting chemicals, particularly bisphenol A (BPA), and its high susceptible exposure- timing, particularly early exposure in lives. Materials and Methods: Female ICR mice were exposed to BPA in utero and in early life (15, 75 and 300 mg/L of drinking water via pregnant mice and lactation). We identified BPA-responsive proteins in mice thyroid by 2D-PAGE, image analyses, and ESI-Q-TOF MS...
March 8, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28274919/%C3%AE-7%C3%AE-1-integrin-regulation-of-gene-transcription-in-skeletal-muscle-following-an-acute-bout-of-eccentric-exercise
#4
Ziad S Mahmassani, Kook Son, Yair Pincu, Michael Munroe, Jenny Drnevich, Jie Chen, Marni D Boppart
The α7β1 integrin is concentrated at the costameres of skeletal muscle and provides a critical link between the actin cytoskeleton and laminin in the basement membrane. We previously have demonstrated that expression of the α7BX2 integrin subunit (MCK:α7BX2) preserves muscle integrity and enhances myofiber cross sectional area following eccentric exercise. The purpose of this study was to utilize gene expression profiling to reveal potential mechanisms by which the α7BX2 integrin contributes to improvements in muscle growth post-exercise...
March 8, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28245171/mir-181a-inhibits-cervical-cancer-development-via-downregulating-grp78
#5
Chengyan Luo, Jiangnan Qiu
Cervical is among one of the top common cancers of women worldwide. Understanding the pathological mechanisms of cervical cancer development is critical for identifying novel targets for cervical cancer treatment. microRNAs (miRs) have various roles in regulating cancer development. Here, we investigated the potential roles of miR-181a and its target in regulating cervical cancer development and chemotherapy resistance. Expression of miR-181a was evaluated and modulated in several human cervical cancer cell lines...
February 13, 2017: Oncology Research
https://www.readbyqxmd.com/read/28243861/potential-contributions-of-heat-shock-proteins-and-related-genes-in-sexual-differentiation-in-yellow-catfish-pelteobagrus-fulvidraco
#6
Yan He, Jie Fang, Liyao Xue, Junjie Wu, Farman Ullah Dawar, Jie Mei
Sex determination and differentiation in ectotherms are very complicated affairs and usually affected by both genetic and environmental factors. Because of their temperature-sensitive expression, heat shock proteins (HSPs) are good candidates for temperature-dependent sex determination (TSD). Similar to most thermosensitive fish species, the male to female ratio increases with temperature in yellow catfish (Pelteobagrus fulvidraco). Yellow catfish is also a type of sexual size dimorphic fish, and the male individuals grow much faster than females of the same age...
February 28, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28220896/mitochondrial-dysregulation-secondary-to-endoplasmic-reticulum-stress-in-autosomal-dominant-tubulointerstitial-kidney-disease-umod-adtkd-umod
#7
Elisabeth Kemter, Thomas Fröhlich, Georg J Arnold, Eckhard Wolf, Rüdiger Wanke
'Autosomal dominant tubulointerstitial kidney disease - UMOD' (ADTKD-UMOD) is caused by impaired maturation and secretion of mutant uromodulin (UMOD) in thick ascending limb of Henle loop (TAL) cells, resulting in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). To gain insight into pathophysiology, we analysed proteome profiles of TAL-enriched outer renal medulla samples from ADTKD-UMOD and control mice by quantitative LC-MS/MS. In total, 212 differentially abundant proteins were identified...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216622/effects-of-gene-polymorphisms-in-the-endoplasmic-reticulum-stress-pathway-on-clinical-outcomes-of-chemoradiotherapy-in-chinese-patients-with-nasopharyngeal-carcinoma
#8
Xiao-Bin Guo, Wan-le Ma, Li-Juan Liu, Yu-Ling Huang, Jing Wang, Li-Hua Huang, Xiang-Dong Peng, Ji-Ye Yin, Jin-Gao Li, Shao-Jun Chen, Guo-Ping Yang, Hui Wang, Cheng-Xian Guo
There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28192616/association-of-ormdl3-with-rhinovirus-induced-endoplasmic-reticulum-stress-and-type-i-interferon-responses-in-human-leukocytes
#9
Yi-Ping Liu, Victoria Rajamanikham, Marissa Baron, Sagar Patel, Sameer K Mathur, Elizabeth A Schwantes, Carole Ober, Daniel J Jackson, James E Gern, Robert F Lemanske, Judith A Smith
BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodeling and hyper-responsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN) regulated chemokine CXCL10...
February 13, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28190459/mutations-in-inpp5k-cause-a-form-of-congenital-muscular-dystrophy-overlapping-marinesco-sj%C3%A3-gren-syndrome-and-dystroglycanopathy
#10
Daniel P S Osborn, Heather L Pond, Neda Mazaheri, Jeremy Dejardin, Christopher J Munn, Khaloob Mushref, Edmund S Cauley, Isabella Moroni, Maria Barbara Pasanisi, Elizabeth A Sellars, R Sean Hill, Jennifer N Partlow, Rebecca K Willaert, Jaipreet Bharj, Reza Azizi Malamiri, Hamid Galehdari, Gholamreza Shariati, Reza Maroofian, Marina Mora, Laura E Swan, Thomas Voit, Francesco J Conti, Yalda Jamshidi, M Chiara Manzini
Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome...
March 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28160139/erratum-to-e1a-mediated-inhibition-of-hspa5-suppresses-cell-migration-and-invasion-in-triple-negative-breast-cancer
#11
Hsin-An Chen, Yi-Wen Chang, Chi-Feng Tseng, Ching-Feng Chiu, Chih-Chen Hong, Weu Wang, Ming-Yang Wang, Michael Hsiao, Jui-Ti Ma, Chung-Hsing Chen, Shih-Sheng Jiang, Chih-Hsiung Wu, Mien-Chie Hung, Ming-Te Huang, Jen-Liang Su
No abstract text is available yet for this article.
February 3, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28148733/dynamic-interaction-and-phospho-proteomics-reveal-lck-as-a-major-signaling-hub-of-cd147-in-t-cells
#12
Verena Supper, Ingrid Hartl, Cyril Boulègue, Anna Ohradanova-Repic, Hannes Stockinger
Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28130223/hspa5-regulates-ferroptotic-cell-death-in-cancer-cells
#13
Shan Zhu, Qiuhong Zhang, Xiaofang Sun, Herbert J Zeh, Michael T Lotze, Rui Kang, Daolin Tang
Ferroptosis is a form of regulated cell death driven by oxidative injury promoting lipid peroxidation, although detailed molecular regulators are largely unknown. Here we show that heat shock 70kDa protein 5 (HSPA5) negatively regulates ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, activating transcription factor 4 (ATF4) resulted in the induction of HSPA5, which in turn bound glutathione peroxidase 4 (GPX4) and protected against GPX4 protein degradation and subsequent lipid peroxidation...
January 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28115289/profibrotic-ihg-1-complexes-with-renal-disease-associated-hspa5-and-trap1-in-mitochondria
#14
Una Bhreathnach, Brenda Griffin, Eoin Brennan, Leah Ewart, Debra Higgins, Madeline Murphy
The highly conserved mitochondrial protein induced in high glucose-1 (IHG-1) functions to maintain mitochondrial quality and is associated with the development of fibrosis in diabetic nephropathy. Towards identifying novel approaches to treating diabetic kidney disease, IHG-1-protein-protein interactions were investigated using epitope-tagged immunoprecipitation analyses followed by mass spectrometry. Here we show that IHG-1 is solely expressed in mitochondria and localised to the inner mitochondrial membrane, the region where mitochondrial reactive oxygen species are generated...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28110670/galnt6-stabilizes-grp78-protein-by-o-glycosylation-and-enhances-its-activity-to-suppress-apoptosis-under-stress-condition
#15
Jiaying Lin, Suyoun Chung, Koji Ueda, Koichi Matsuda, Yusuke Nakamura, Jae-Hyun Park
We previously reported that overexpression of an O-type glycosyltransferase, GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) played critical roles in mammary carcinogenesis. To further investigate the biological function of GALNT6, we screened a substrate protein(s) of GALNT6 using a VVA (Vicia villosa agglutinin) lectin (specific to GalNAc-Ser/Thr) pull-down method followed by mass spectrometry analysis. Here we report GRP78 (glucose-regulated protein 78, also known as HSPA5, heat shock 70 kDa protein 5), which is highly expressed in cancer cells and indicated to play important roles in various cellular processes including ER (endoplasmic reticulum) stress and autophagy, as a novel substrate of GALNT6...
January 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27892644/saliva-protein-biomarkers-to-detect-oral-squamous-cell-carcinoma-oscc
#16
R Nagler
In a recent study published in the Proceedings of the National Academy of Sciences of the U.S.A., Jau-Song Yu et al reported of their generated four-protein biomarker panel consisting of MMP1, KNG1, ANXA2, and HSPA5, as based on a risk-score scheme they established (Yu et al, 2016). This panel showed high sensitivity (87.5%) and specificity (80.5%) values in a test set to distinguish OSCC patients' saliva samples from non-OSCC patients' saliva samples. The risk score >0.4 detected 84% of the stage I OSCCs and a significant portion (42%) of the high-risk, visible, oral potentially-malignant disorders (OPMDs)...
November 28, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27881906/genetic-and-immunohistochemical-analysis-of-hspa5-in-mouse-and-human-retinas
#17
Sumana R Chintalapudi, XiaoFei Wang, Huiling Li, Yin H Chan Lau, Robert W Williams, Monica M Jablonski
PURPOSE: Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27791469/new-anti-cancer-molecules-targeting-hspa5-bip-to-induce-endoplasmic-reticulum-stress-autophagy-and-apoptosis
#18
Michaël Cerezo, Stéphane Rocchi
Treatment of melanoma has significantly advanced over the last decade, with the development of targeted therapies against the MAPK pathway and immunotherapies to reactivate antitumor immunity. Unfortunately, currently more than 50% of patients are in treatment failure. Thus, identification of new common cellular vulnerability among melanoma cells is an urgent need and will help in the discovery of more efficient treatments against melanoma. We have focused our study on protein processing and have identified a new compound, HA15, targeting HSPA5/BiP, the master regulator of the unfolded protein response (UPR)...
January 2, 2017: Autophagy
https://www.readbyqxmd.com/read/27756316/integrins-are-not-essential-for-entry-of-coxsackievirus-a9-into-sw480-human-colon-adenocarcinoma-cells
#19
Outi Heikkilä, Pirjo Merilahti, Marika Hakanen, Eveliina Karelehto, Jonna Alanko, Maria Sukki, Saija Kiljunen, Petri Susi
BACKGROUND: Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9...
October 18, 2016: Virology Journal
https://www.readbyqxmd.com/read/27746171/characterization-of-cadmium-chloride-induced-bip-accumulation-in-xenopus-laevis-a6-kidney-epithelial-cells
#20
Cody S Shirriff, John J Heikkila
Endoplasmic reticulum (ER) stress can result in the accumulation of unfolded/misfolded protein in the ER lumen, which can trigger the unfolded protein response (UPR) resulting in the activation of various genes including immunoglobulin-binding protein (BiP; also known as glucose-regulated protein 78 or HSPA5). BiP, an ER heat shock protein 70 (HSP70) family member, binds to unfolded protein, inhibits their aggregation and re-folds them in an ATP-dependent manner. While cadmium, an environmental contaminant, was shown to induce the accumulation of HSP70 in vertebrate cells, less information is available regarding the effect of this metal on BiP accumulation or function...
January 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
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