3,232 results match your criteria knockdown er+

Atherosclerosis-associated hepatic secretion of VLDL but not PCSK9 is dependent on cargo receptor protein Surf4.

J Lipid Res 2021 Jun 9:100091. Epub 2021 Jun 9.

Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Plasma LDL is produced from catabolism of VLDL and is cleared from circulation mainly via the hepatic LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDLR degradation, increasing plasma LDL cholesterol levels. Circulating PCSK9 is mainly secreted by the liver, while VLDL is exclusively secreted by hepatocytes. Read More

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ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron.

Acta Pharmacol Sin 2021 Jun 10. Epub 2021 Jun 10.

Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China.

Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and HO via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and HO. Read More

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Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2α signaling pathway in IPEC-J2 cells.

J Anim Sci Biotechnol 2021 Jun 11;12(1):69. Epub 2021 Jun 11.

Institute of Animal Nutrition, Sichuan Agricultural University, Huimin Road 211#, Chengdu, Sichuan Province, 611130, P. R. China.

Background: Rotavirus (RV) is a major pathogen that causes severe gastroenteritis in infants and young animals. Endoplasmic reticulum (ER) stress and subsequent apoptosis play pivotal role in virus infection. However, the protective mechanisms of intestinal damage caused by RV are poorly defined, especially the molecular pathways related to enterocytes apoptosis. Read More

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CHOP Regulates Endoplasmic Reticulum Stress-Mediated Hepatoxicity Induced by Monocrotaline.

Front Pharmacol 2021 24;12:685895. Epub 2021 May 24.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Monocrotaline (MCT), a pyrrolizidine alkaloid, is the major toxin in , which causes cell apoptosis in humans and animals. It has been reported that the liver is a vulnerable target of MCT. However, the exact molecular mechanism of the interaction between endoplasmic reticulum (ER) stress and liver injury induced by MCT is still unclear. Read More

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Combined inhibition of DDR1 and CDK4/6 induces synergistic effects in ER-positive, HER2-negative breast cancer with PIK3CA/AKT1 mutations.

Oncogene 2021 Jun 9. Epub 2021 Jun 9.

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Molecular alterations in the PI3K/AKT pathway occur frequently in hormone receptor-positive breast tumors. Patients with ER-positive, HER2-negative metastatic breast cancer are often treated with CDK4/6 inhibitors such as palbociclib in combination with endocrine therapy. Although this is an effective regimen, most patients ultimately progress. Read More

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A role for the ribosome-associated complex in activation of the IRE1 branch of UPR.

Cell Rep 2021 Jun;35(10):109217

Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, USA; CFFT Lab, Cystic Fibrosis Foundation, Lexington, MA 02421, USA. Electronic address:

The ubiquitous ribosome-associated complex (RAC) is a chaperone that spans ribosomes, making contacts near both the polypeptide exit tunnel and the decoding center, a position prime for sensing and coordinating translation and folding. Loss of RAC is known to result in growth defects and sensitization to translational and osmotic stresses. However, the physiological substrates of RAC and the mechanism(s) by which RAC is involved in responding to specific stresses in higher eukaryotes remain obscure. Read More

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PELP1/SRC-3-dependent regulation of metabolic PFKFB kinases drives therapy resistant ER breast cancer.

Oncogene 2021 Jun 8. Epub 2021 Jun 8.

Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.

Recurrence of metastatic breast cancer stemming from acquired endocrine and chemotherapy resistance remains a health burden for women with luminal (ER) breast cancer. Disseminated ER tumor cells can remain viable but quiescent for years to decades. Contributing factors to metastatic spread include the maintenance and expansion of breast cancer stem cells (CSCs). Read More

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Circular RNA circ-FAM158A promotes retinoblastoma progression by regulating miR-138-5p/SLC7A5 axis.

Exp Eye Res 2021 Jun 5:108650. Epub 2021 Jun 5.

Department of Ophthalmology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, No.250 East Street, Quanzhou 362000, Fujian Province, China. Electronic address:

Background: Mounting evidence has shown that circular RNAs (circRNAs) have vital roles in human cancers, including retinoblastoma (RB). The purpose of this study was to investigate the exact roles and underlying mechanism of circRNA ER membrane protein complex subunit 9 (circ-FAM158A) in RB.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the expression levels of circ-FAM158A, miR-138-5p and solute carrier family 7 member 5 (SLC7A5). Read More

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SMYD3-PARP16 axis accelerates unfolded protein response and mediates neointima formation.

Acta Pharm Sin B 2021 May 15;11(5):1261-1273. Epub 2020 Dec 15.

Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China.

Neointimal hyperplasia after vascular injury is a representative complication of restenosis. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) is involved in the pathogenesis of vascular intimal hyperplasia. PARP16, a member of the poly(ADP-ribose) polymerases family, is correlated with the nuclear envelope and the ER. Read More

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lncRNA Xist regulates sevoflurane-induced social and emotional impairment by modulating miR-98-5p/EDEM1 signaling axis in neonatal mice.

Mol Ther Nucleic Acids 2021 Jun 16;24:939-950. Epub 2021 Apr 16.

Department of Anesthesiology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Long non-coding RNA (lncRNA) X-inactive specific transcript (Xist) is involved in apoptosis and inflammatory injury. This study aimed to assess the role of lncRNA Xist in sevoflurane-induced social and emotional impairment and neuronal apoptosis in neonatal mice and hippocampal neuronal cells. The performance in social and emotional tests and the expression levels of lncRNA Xist and microRNA (miR)-98-5p after sevoflurane exposure were measured. Read More

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Boosting immune surveillance by low-dose PI3K inhibitor facilitates early intervention of breast cancer.

Am J Cancer Res 2021 15;11(5):2005-2024. Epub 2021 May 15.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center Houston, Texas, USA.

Prevention of estrogen receptor-negative (ER-) breast cancer is an unmet challenge, although tamoxifen and aromatase inhibitors can successfully decrease the incidence of ER-positive (ER+) breast cancer. PI3K pathway activation has been detected in tamoxifen-resistant ER- breast lesions of patients. Here, we further ratified that the PI3K pathway is significantly activated in premalignant ER- breast lesions compared with paired normal tissues of patients, which prompted our assessment of targeting PI3K on inhibition of ER- mammary tumor initiation and progression. Read More

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The ERβ-CXCL19/CXCR4-NFκB pathway is critical in mediating the E2-induced inflammation response in the orange-spotted grouper (Epinephelus coioides).

J Steroid Biochem Mol Biol 2021 Jun 4;212:105926. Epub 2021 Jun 4.

College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, Guangzhou, 510642, China. Electronic address:

The main physiological function of 17β-estradiol (E2) in vertebrates is to regulate sexual development and reproduction. In fish, especially hermaphroditic fish, estrogen is often used to aid reproduction, but it also can trigger an inflammatory response. However, the molecular mechanism for this E2-induced inflammatory reaction is not clear. Read More

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The ameliorative effect of terpinen-4-ol on ER stress-induced vascular calcification depends on SIRT1-mediated regulation of PERK acetylation.

Pharmacol Res 2021 Jun 2:105629. Epub 2021 Jun 2.

The State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University, University Town, Guian New District, Guizhou, China; Department of Pharmacology of Materia Medica (the High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, the High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province), Guizhou Medical University, University Town, Guian New District, Guizhou, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guizhou, China. Electronic address:

Endoplasmic reticulum (ER) stress-mediated phenotypic switching of vascular smooth muscle cells (VSMCs) is key to vascular calcification (VC) in patients with chronic kidney disease (CKD). Studies have shown that activation/upregulation of SIRT1 has a protective effect on CKD-VC. Meanwhile, although terpinen-4-ol has been shown to exert a protective effect against cardiovascular disease, its role and underlying mechanism in VC remain unclear. Read More

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DDIT3/CHOP promotes autophagy in chondrocytes via SIRT1-AKT pathway.

Biochim Biophys Acta Mol Cell Res 2021 Jun 2;1868(9):119074. Epub 2021 Jun 2.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, Hubei, China. Electronic address:

Endoplasmic reticulum (ER) stress can initiate autophagy via unfolded protein response (UPR). As a key downstream gene of UPR, DDIT3/CHOP is expressed in chondrocytes. However, the regulation mechanism of DDIT3/CHOP on autophagy in chondrocytes remains unclear. Read More

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TNFα Enhances Tamoxifen Sensitivity through Dissociation of ERα-p53-NCOR1 Complexes in ERα-Positive Breast Cancer.

Cancers (Basel) 2021 May 26;13(11). Epub 2021 May 26.

Asan Medical Center, Department of Biomedical Sciences, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea.

Tamoxifen is widely used as a medication for estrogen receptor α (ERα)-positive breast cancer, despite the ~50% incidence of tamoxifen resistance. To overcome such resistance, combining tamoxifen with other agents is considered an effective approach. Here, through in vitro studies with ER-positive MCF7 cells and ER-negative MDA-MB-231 cells, validated by the use of xenograft mice, we investigated the potential of tumor necrosis factor α (TNFα) to enhance tamoxifen sensitivity and identified NCOR1 as a key downstream regulator. Read More

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PERK/ATF4-Dependent ZFAS1 Upregulation Is Associated with Sorafenib Resistance in Hepatocellular Carcinoma Cells.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Department of Surgery, MacKay Memorial Hospital, Taipei 10449, Taiwan.

Sorafenib, a multi-kinase inhibitor, is the first-line treatment for advanced hepatocellular carcinoma (HCC) patients. However, this drug only provides a short improvement of patients' overall survival, and drug resistance is commonly developed. Thus, the identification of resistant factor(s) or biomarker(s) is needed to develop more efficient therapeutic strategies. Read More

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Enhanced autophagy suppresses inflammation-mediated bone loss through ROCK1 signaling in bone marrow mesenchymal stem cells.

Cells Dev 2021 May 28;167:203687. Epub 2021 May 28.

Department of Oral and Maxillofacial Surgery, Key Laboratory of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Huangdao District, 266555 Qingdao, Shandong, China. Electronic address:

Bone marrow mesenchymal stem cells (BMSCs) have strong proliferative ability and multi-directional differentiation potential. Osteoarthritis is a degenerative joint disease that is closely related to the loss of osteogenic differentiation function of BMSCs. Autophagy, plays a crucial role in the maintenance of cellular functions, but its regulatory mechanism during the osteogenic differentiation of BMSCs remains unclear. Read More

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A novel XBP1 variant is highly enriched in cancer tissues and is specifically required for cancer cell survival.

Biochem Biophys Res Commun 2021 Jul 24;562:69-75. Epub 2021 May 24.

Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Program in Oncology, UM Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. Electronic address:

XBP1 is a basic leucine zipper (bZIP) transcription factor and a key mediator of the endoplasmic reticulum (ER) stress-activated unfolded protein response (UPR). XBP1-mediated transcription facilitates cell adaptation to ER stress and also promotes tumor progression, while suppressing anti-tumor immunity. Here we report a novel XBP1 variant, namely XBP1 variant 1 (XBP1v1, Xv1 for short), that is specifically required for survival of cancer cells. Read More

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The Downregulation of ADAM17 Exerts Protective Effects against Cardiac Fibrosis by Regulating Endoplasmic Reticulum Stress and Mitophagy.

Oxid Med Cell Longev 2021 6;2021:5572088. Epub 2021 May 6.

Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: A disintegrin and metalloproteinase 17 (ADAM17) is a transmembrane protein that is widely expressed in various tissues; it mediates the shedding of many membrane-bound molecules, involving cell-cell and cell-matrix interactions. We investigated the role of ADAM17 within mouse cardiac fibroblasts (mCFs) in heart fibrosis.

Methods: mCFs were isolated from the hearts of neonatal mice. Read More

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Loss of polarity protein Par3 is mediated by transcription factor Sp1 in breast cancer.

Biochem Biophys Res Commun 2021 Jul 21;561:172-179. Epub 2021 May 21.

NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 130 Dong'an Road, Xuhui District, Shanghai, 200032, PR China. Electronic address:

Loss of polarity protein Par3 promotes breast cancer tumorigenesis and metastasis. The underlying molecular mechanisms of Par3 down-regulation and related prognostic significance in breast cancer remain unclear. Here, we discovered that Par3 down-regulation was associated with shorter relapse-free survival in Luminal A subtype of breast cancer. Read More

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NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes.

EMBO J 2021 May 21:e105990. Epub 2021 May 21.

Department of Physiology and Membrane Biology, University of California, Davis, CA, USA.

Cholesterol and phosphoinositides (PI) are two critically important lipids that are found in cellular membranes and dysregulated in many disorders. Therefore, uncovering molecular pathways connecting these essential lipids may offer new therapeutic insights. We report that loss of function of lysosomal Niemann-Pick Type C1 (NPC1) cholesterol transporter, which leads to neurodegenerative NPC disease, initiates a signaling cascade that alters the cholesterol/phosphatidylinositol 4-phosphate (PtdIns4P) countertransport cycle between Golgi-endoplasmic reticulum (ER), as well as lysosome-ER membrane contact sites (MCS). Read More

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ER membrane protein complex 1 interacts with STIM1 and regulates store-operated Ca2+ entry.

J Biochem 2021 May 20. Epub 2021 May 20.

Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Store-operated calcium entry (SOCE) is the process by which the emptying of endoplasmic reticulum (ER) Ca2+ stores causes an influx of Ca2+ across the plasma membrane. It is the major Ca2+ influx pathway in non-excitable cells and has a wide array of physiological functions. Upon store depletion, stromal interaction molecule 1 (STIM1), an ER calcium sensor relocates into discrete puncta at the ER-plasma membrane junction region, which results in the coupling of Ca2+ channels to initiate SOCE. Read More

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TASP1 Promotes Proliferation and Migration in Gastric Cancer via EMT and AKT/P-AKT Pathway.

J Immunol Res 2021 29;2021:5521325. Epub 2021 Apr 29.

The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, No. 62, Huaihai Road (S.), Huaian 223002, China.

Threonine aspartase 1 (TASP1) was reported to function in the development of cancer. However, the regulatory mechanism of TASP1 in gastric cancer (GC) remains unclear. In this study, we determined the expression of TASP1 in tissues of GC patients, GC cells by qRT-PCR, and western blot and assessed the relationship between TASP1 and GC cell proliferation and migration via CCK-8 and transwell assay. Read More

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Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer.

Nat Commun 2021 05 19;12(1):2940. Epub 2021 May 19.

Tumor Microenvironment and Cancer Immunology, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Resistance to endocrine treatment occurs in ~30% of ER breast cancer patients resulting in ~40,000 deaths/year in the USA. Preclinical studies strongly implicate activation of growth factor receptor, HER2 in endocrine treatment resistance. However, clinical trials of pan-HER inhibitors in ER/HER2 patients have disappointed, likely due to a lack of predictive biomarkers. Read More

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Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN.

Cell Death Dis 2021 May 18;12(6):502. Epub 2021 May 18.

Department of Breast-Thyroid-Surgery and Cancer Center, Xiang'an Hospital of Xiamen University, 2000 East Xiang'an Road, Xiamen, China.

Notch receptors (Notch1-4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. Read More

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MMP-3 plays a major role in calcium pantothenate-promoted wound healing after fractional ablative laser treatment.

Lasers Med Sci 2021 May 14. Epub 2021 May 14.

Department of Dermatology and Allergology, Medical Faculty RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.

Ablative fractional laser treatment leads to a loss of matrix metalloproteinase-3 (MMP-3) expression; therefore, in the present in vitro study, we addressed the role of MMP-3 and its regulation by calcium pantothenate in wound healing processes at the molecular level. Utilizing confocal laser microscopy, we investigated MMP-3 protein expression in fractional ablative CO laser-irradiated skin models. In addition, we established full-thickness 3D skin models using fibroblasts and keratinocytes with a MMP-3 knockdown that were irradiated with a fractional ablative Er:YAG laser to set superficial injuries with standardized dimensions and minimal thermal damage to the surrounding tissue. Read More

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Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression.

Ann Transl Med 2021 Apr;9(8):636

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Inositol-requiring enzyme 1 (IRE1) plays a critical role in attenuating endoplasmic reticulum (ER) stress associated with renal injury which may also be a factor in diabetic nephropathy (DN). Alcohol dehydrogenase type I (ADH1) activity is prominent in the kidney, ADH1 activity is also reported to exert protective effects against ER stress that are not caused by alcohol consumption. However, the role of IRE1 in DN and the correlation between IRE1 and ADH1 activity remain unclear. Read More

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ESM1 promotes triple-negative breast cancer cell proliferation through activating AKT/NF-κB/Cyclin D1 pathway.

Ann Transl Med 2021 Apr;9(7):533

College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.

Background: Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer that tests negative for PR, ER and excess HER2 protein. TNBC has a greater progression potential with poorer prognosis, compared with other types of breast cancer. Endothelial cell-specific molecule 1 (ESM1), also known as endocan, is overexpressed in various cancers including breast cancer and may play an important role in cancer progression. Read More

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Endoplasmic reticulum stress regulates the intestinal stem cell state through CtBP2.

Sci Rep 2021 May 10;11(1):9892. Epub 2021 May 10.

Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, Amsterdam, The Netherlands.

Enforcing differentiation of cancer stem cells is considered as a potential strategy to sensitize colorectal cancer cells to irradiation and chemotherapy. Activation of the unfolded protein response, due to endoplasmic reticulum (ER) stress, causes rapid stem cell differentiation in normal intestinal and colon cancer cells. We previously found that stem cell differentiation was mediated by a Protein kinase R-like ER kinase (PERK) dependent arrest of mRNA translation, resulting in rapid protein depletion of WNT-dependent transcription factor c-MYC. Read More

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Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons.

J Vis Exp 2021 04 24(170). Epub 2021 Apr 24.

Instituto de Investigación Médica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba;

The accumulation of unfolded proteins within the endoplasmic reticulum (ER), caused by any stress condition, triggers the unfolded protein response (UPR) through the activation of specialized sensors. UPR attempts first to restore homeostasis; but if damage persists the signaling induces apoptosis. There is increasing evidence that sustained and unresolved ER stress contributes to many pathological conditions including neurodegenerative diseases. Read More

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