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https://www.readbyqxmd.com/read/28619709/loss-of-fam46c-promotes-cell-survival-in-myeloma
#1
Yuan Xiao Zhu, Chang-Xin Shi, Laura A Bruins, Patrick Jedlowski, Xuewei Wang, K Martin Kortüm, Moulun Luo, Jonathan Ahmann, Esteban Braggio, A Keith Stewart
FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis has not been determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity, indicating a survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, and MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP Furthermore, pathway analysis suggests that enforced FAM46C expression activated the unfolded protein response (UPR) pathway and induced mitochondrial dysfunction...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28601093/granulin-epithelin-precursor-interacts-with-78-kda-glucose-regulated-protein-in-hepatocellular-carcinoma
#2
Chi Wai Yip, Ching Yan Lam, Terence C W Poon, Tan To Cheung, Phyllis F Y Cheung, Sze Wai Fung, Xiao Qi Wang, Idy C Y Leung, Linda W C Ng, Chung Mau Lo, George S W Tsao, Siu Tim Cheung
BACKGROUND: Granulin-epithelin precursor (GEP) is a secretory growth factor, which has been demonstrated to control cancer growth, invasion, drug resistance and immune escape. Our previous studies and others also demonstrated its potential in targeted therapy. Comprehensive characterization of GEP partner on cancer cells are warranted. We have previously shown that GEP interacted with heparan sulfate on the surface of liver cancer cells and the interaction is crucial for GEP-mediated signaling transduction...
June 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28534368/study-on-the-molecular-mechanism-of-rac3-on-regulating-autophagy-in-human-lung-cancer-cells
#3
Xuyang Xiao, Gebang Wang, Hongxu Liu
PURPOSE: Rac3 plays an important role in regulating tumorigenesis. Autophagy plays a vital role in tumorigenesis and tumor progression. The relationship between the two remains unclear. The objective of the present study was to determine the specific molecular mechanism of intracellular Rac3 in regulating autophagy and reveal the relationship between tumor cell autophagy and apoptosis. METHODS: A laser confocal microscope was used to photograph the accumulated EGFP-MAP1LC3 spots for investigating the relationship between Rac3 and autophagy at the cellular level...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28461470/grp78-haploinsufficiency-suppresses-acinar-to-ductal-metaplasia-signaling-and-mutant-kras-driven-pancreatic-tumorigenesis-in-mice
#4
Jieli Shen, Dat P Ha, Genyuan Zhu, Daisy F Rangel, Agnieszka Kobielak, Parkash S Gill, Susan Groshen, Louis Dubeau, Amy S Lee
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease in critical need of new therapeutic strategies. Here, we report that the stress-inducible 78-kDa glucose-regulated protein (GRP78/HSPA5), a key regulator of endoplasmic reticulum homeostasis and PI3K/AKT signaling, is overexpressed in the acini and PDAC of Pdx1-Cre;Kras(G12D/+);p53(f/+) (PKC) mice as early as 2 mo, suggesting that GRP78 could exert a protective effect on acinar cells under stress, as during PDAC development. The PKC pancreata bearing wild-type Grp78 showed detectable PDAC by 3 mo and rapid subsequent tumor growth...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28393315/identification-and-characterization-of-biomarkers-and-their-functions-for-lapatinib-resistant-breast-cancer
#5
Liang Zhang, Yi Huang, Wenlei Zhuo, Yi Zhu, Bo Zhu, Zhengtang Chen
Lapatinib, a novel oral dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways, has presented beneficial effects on breast cancer with positive HER2. However, its efficacy is largely limited by the occurrence of acquired drug resistance. In this study, we aimed to explore the underlying molecular mechanisms of Lapatinib resistance using bioinformatics strategies. The gene expression profile of SKBR3-R (acquired Lapatinib-resistant) and SKBR3 (Lapatinib-sensitive) cell line was downloaded from gene expression omnibus database...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28363780/mir-199a-5p-and-mir-495-target-grp78-within-upr-pathway-of-lung-cancer
#6
Azam Ahmadi, Behzad Khansarinejad, Saman Hosseinkhani, Mostafa Ghanei, Seyed Javad Mowla
INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer. One of the signal transduction pathways related to NSCLC is Unfolded Protein Response (UPR), which is mainly regulated by GRP78 (HSPA5, Gene ID: 3309). The aim of this study was to employ bioinformatics tools to predict microRNAs (miRNAs) affecting GRP78 expression, experimentally validate interaction of these miRNAs with GRP78 and also evaluating the expression correlation of GRP78 and its predicted miRNAs in clinical samples...
July 15, 2017: Gene
https://www.readbyqxmd.com/read/28332555/loxl2-drives-epithelial-mesenchymal-transition-via-activation-of-ire1-xbp1-signalling-pathway
#7
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
#8
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene 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...
June 30, 2017: Gene
https://www.readbyqxmd.com/read/28279065/proteomic-biomarkers-for-bisphenol-a-early-exposure-and-women-s-thyroid-cancer
#9
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
#10
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 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 after exercise...
May 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28245171/mir-181a-inhibits-cervical-cancer-development-via-downregulating-grp78
#11
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
#12
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
#13
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
#14
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...
April 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-leucocytes
#15
Y-P Liu, V Rajamanikham, M Baron, S Patel, S K Mathur, E A Schwantes, C Ober, D J Jackson, J E Gern, R F Lemanske, J 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 remodelling and hyperresponsiveness. 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...
March 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
#16
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
#17
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
#18
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
#19
Shan Zhu, Qiuhong Zhang, Xiaofan 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 heatshock 70-kDa 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...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28115289/profibrotic-ihg-1-complexes-with-renal-disease-associated-hspa5-and-trap1-in-mitochondria
#20
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
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