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https://www.readbyqxmd.com/read/29133591/chemokine-signaling-facilitates-early-stage-breast-cancer-survival-and-invasion-through-fibroblast-dependent-mechanisms
#1
Gage Brummer, Diana S Acevedo, Qingting Hu, Mike Portsche, Wei Fang, Min Yao, Brandon Zinda, Megan Myers, Nehemiah S Alvarez, Patrick Fields, Yan Hong, Fariba Behbod, Nikki Cheng
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Over-treatment and under-treatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29126758/maspin-expression-and-subcellular-localization-in-invasive-ductal-carcinoma-of-the-breast-prognostic-significance-and-relation-to-microvessel-density
#2
Duaa S Helal, Dina M El-Guindy
Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor...
November 7, 2017: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/29118397/the-kunitz-domain-i-of-hepatocyte-growth-factor-activator-inhibitor-2-inhibits-matriptase-activity-and-invasive-ability-of-human-prostate-cancer-cells
#3
Shang-Ru Wu, Chen-Hsin Teng, Ya-Ting Tu, Chun-Jung Ko, Tai-Shan Cheng, Shao-Wei Lan, Hsin-Ying Lin, Hsin-Hsien Lin, Hsin-Fang Tu, Pei-Wen Hsiao, Hsiang-Po Huang, Chung-Hsin Chen, Ming-Shyue Lee
Dysregulation of pericellular proteolysis is often required for tumor invasion and cancer progression. It has been shown that down-regulation of hepatocyte growth factor activator inhibitor-2 (HAI-2) results in activation of matriptase (a membrane-anchored serine protease), human prostate cancer cell motility and tumor growth. In this study, we further characterized if HAI-2 was a cognate inhibitor for matriptase and identified which Kunitz domain of HAI-2 was required for inhibiting matriptase and human prostate cancer cell motility...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115822/single-quantum-dot-based-nanosensor-for-sensitive-detection-of-o-glcnac-transferase-activity
#4
Juan Hu, Yueying Li, Ying Li, Bo Tang, Chun-Yang Zhang
Protein glycosylation is a ubiquitous post-translational modification that plays crucial roles in modulating biological recognition events in development and physiology. Human O-GlcNAc transferase (OGT) is an intracellular enzyme responsible for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, and the deregulation of OGT activity occurs in cancer, diabetes and neurodegenerative disease. Here, we develop a single quantum dot (QD)-based nanosensor for sensitive OGT assay. We design a Cy5/biotin-modified peptide with a serine hydroxyl group for sensing OGT and a protease site adjacent to the glycosylation site for proteinase cleavage, with a universal nonradioactive UDP-GlcNAc as the sugar donor and a Cy5/biotin-modified peptide as the substrate...
November 8, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29113189/the-oncogenic-transcription-factor-erg-represses-the-transcription-of-the-tumour-suppressor-gene-pten-in-prostate-cancer-cells
#5
Patricia Adamo, Sean Porazinski, Shavanthi Rajatileka, Samantha Jumbe, Rachel Hagen, Man-Kim Cheung, Ian Wilson, Michael R Ladomery
The oncogene ETS-related gene (ERG) encodes a transcription factor with roles in the regulation of haematopoiesis, angiogenesis, vasculogenesis, inflammation, migration and invasion. The ERG oncogene is activated in >50% of prostate cancer cases, generally through a gene fusion with the androgen-responsive promoter of transmembrane protease serine 2. Phosphatase and tensin homologue (PTEN) is an important tumour suppressor gene that is often inactivated in cancer. ERG overexpression combined with PTEN inactivation or loss is often associated with aggressive prostate cancer...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29107700/general-and-modular-strategy-for-designing-potent-selective-and-pharmacologically-compliant-inhibitors-of-rhomboid-proteases
#6
Anežka Tichá, Stancho Stanchev, Kutti R Vinothkumar, David C Mikles, Petr Pachl, Jakub Began, Jan Škerle, Kateřina Švehlová, Minh T N Nguyen, Steven H L Verhelst, Darren C Johnson, Daniel A Bachovchin, Martin Lepšík, Pavel Majer, Kvido Strisovsky
Rhomboid-family intramembrane proteases regulate important biological processes and have been associated with malaria, cancer, and Parkinson's disease. However, due to the lack of potent, selective, and pharmacologically compliant inhibitors, the wide therapeutic potential of rhomboids is currently untapped. Here, we bridge this gap by discovering that peptidyl α-ketoamides substituted at the ketoamide nitrogen by hydrophobic groups are potent rhomboid inhibitors active in the nanomolar range, surpassing the currently used rhomboid inhibitors by up to three orders of magnitude...
October 12, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29100036/nafamostat-mesilate-a-serine-protease-inhibitor-suppresses-interferon-gamma-induced-up-regulation-of-programmed-cell-death-ligand-1-in-human-cancer-cells
#7
Sadamu Homma, Kazumi Hayashi, Kosaku Yoshida, Yukiko Sagawa, Yuko Kamata, Masaki Ito
Programmed cell death ligand-1 (PD-L1) plays a pivotal role in the suppression of antitumour immunity by binding to programmed cell death-1 (PD-1) on tumouricidal cytotoxic T lymphocytes (CTLs), rendering them inactive. As blockade of PD-1/PD-L1 interaction by the monoclonal antibodies induced effective T cell-mediated antitumour response, suppression of PD-L1 expression in tumour cells by the chemical agent might contribute to treatment against malignant tumours. Nafamostat mesilate (NM), a serine protease inhibitor that is frequently used in the clinic, potently suppressed interferon-gamma (IFN-gamma)-induced up-regulation of PD-L1 in cultured human lung cancer cells (HLC-1) at both the messenger RNA (mRNA) and protein levels...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29084210/zeb1-repressed-micrornas-inhibit-autocrine-signaling-that-promotes-vascular-mimicry-of-breast-cancer-cells
#8
E M Langer, N D Kendsersky, C J Daniel, G M Kuziel, C Pelz, K M Murphy, M R Capecchi, R C Sears
During normal tumor growth and in response to some therapies, tumor cells experience acute or chronic deprivation of nutrients and oxygen and induce tumor vascularization. While this occurs predominately through sprouting angiogenesis, tumor cells have also been shown to directly contribute to vessel formation through vascular mimicry (VM) and/or endothelial transdifferentiation. The extrinsic and intrinsic mechanisms underlying tumor cell adoption of endothelial phenotypes, however, are not well understood...
October 30, 2017: Oncogene
https://www.readbyqxmd.com/read/29054266/circulating-peptidome-and-tumor-resident-proteolysis
#9
Jia Fan, Bo Ning, Christopher J Lyon, Tony Y Hu
Mammalian proteases segregate into several distinct protein families that employ different functional domains to hydrolyze peptides bonds with different specificities and affinities. These enzymes play central roles in critical cellular and systemic processes, including regulation of cell growth, differentiation, homeostasis, and apoptosis; and cancer initiation, progression, and metastasis. Human proteases segregate into five distinct catalytic classes; the metalloprotease, serine protease, and cysteine protease families have the most members, while the aspartic and threonine peptidase families have relatively few examples...
2017: Enzymes
https://www.readbyqxmd.com/read/29046355/matrix-metalloproteinase-7-induces-homotypic-tumor-cell-aggregation-via-proteolytic-cleavage-of-the-membrane-bound-kunitz-type-inhibitor-hai-1
#10
Tomohiro Ishikawa, Yayoi Kimura, Hisashi Hirano, Shouichi Higashi
Matrix metalloproteinase-7 (MMP-7) plays important roles in tumor progression and metastasis. Our previous studies have demonstrated that MMP-7 binds to colon cancer cells via cell surface-bound cholesterol sulfate and induces significant cell aggregation by cleaving cell-surface protein(s). These aggregated cells exhibit a dramatically enhanced metastatic potential. However, the molecular mechanism inducing this cell-cell adhesion through the proteolytic action of MMP-7 remained to be clarified. Here, we explored MMP-7 substrates on cell surface; the proteins on cell surface were first biotinylated and a labeled protein fragment specifically released from the cells after MMP-7-treatment was analyzed using LC-MS/MS...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29029529/the-roles-of-maspin-expression-in-gastric-cancer-a-meta-and-bioinformatics-analysis
#11
Hua-Chuan Zheng, Bao-Cheng Gong
Maspin is a mammary serine protease inhibitor that is encoded by human SERPINB5 gene, and inhibits invasion and metastasis of cancer cells as a tumor suppressor. We performed a systematic meta- and bioinformatics analysis through multiple online databases up to Feb 10, 2017. We found down-regulated maspin expression in gastric cancer, compared with normal mucosa and dysplasia (p < 0.05). Maspin expression was negatively correlated with depth of invasion, TNM staging and dedifferentiation of gastric cancer (p < 0...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28983631/integrated-analysis-reveals-candidate-genes-and-transcription-factors-in-lung-adenocarcinoma
#12
Baiwang Chen, Shuhong Gao, Changwei Ji, Ge Song
Lung adenocarcinoma is the most common type of non‑small cell lung cancer in Asia. Therefore, it is important to improve understanding of the underlying transcriptional regulatory mechanisms involved. The present study aimed to identify potential candidate genes and transcription factors (TFs) associated with the disease. Four gene expression profiles were downloaded from the Gene Expression Omnibus database, which included 141 lung adenocarcinoma patients and 191 healthy controls. The differentially expressed genes (DEGs) were screened out and functional annotation was performed...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28977906/trypsin-protease-activated-receptor-2-signaling-contributes-to-pancreatic-cancer-pain
#13
Jiao Zhu, Xue-Rong Miao, Kun-Ming Tao, Hai Zhu, Zhi-Yun Liu, Da-Wei Yu, Qian-Bo Chen, Hai-Bo Qiu, Zhi-Jie Lu
Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970566/selective-homogeneous-assay-for-circulating-endopeptidase-fibroblast-activation-protein-fap
#14
Travis W Bainbridge, Diana Ronai Dunshee, Noelyn M Kljavin, Nicholas J Skelton, Junichiro Sonoda, James A Ernst
Fibroblast Activation Protein (FAP) is a membrane-bound serine protease whose expression is often elevated in activated fibroblasts associated with tissue remodeling in various common diseases such as cancer, arthritis and fibrosis. Like the closely related dipeptidyl peptidase DPPIV, the extracellular domain of FAP can be released into circulation as a functional enzyme, and limited studies suggest that the circulating level of FAP correlates with the degree of tissue fibrosis. Here we describe a novel homogeneous fluorescence intensity assay for circulating FAP activity based on a recently identified natural substrate, FGF21...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28970170/microbial-serine-protease-inhibitors-and-their-therapeutic-applications
#15
REVIEW
B S Harish, Kiran Babu Uppuluri
Serine protease inhibitors, inhibit serine proteases either partially or completely after forming complexes with their respective proteases. Protease actions are significant for many physiological pathways found in living forms and any anomalies may lead to numerous physiological complications. Each cell or organism has its own mechanism for controlling these protease actions. It is often regulated by the action of inhibitors or activators. Among the proteases, serine proteases are the most common that are involved in many life and death processes...
September 29, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28968951/estradiol-er%C3%AE-2-signaling-axis-confers-growth-and-migration-of-crpc-cells-through-tmprss2-etv5-gene-fusion
#16
Hogyoung Kim, Amrita Datta, Sudha Talwar, Sarmad N Saleem, Debasis Mondal, Asim B Abdel-Mageed
Estrogen receptor beta (ERβ) splice variants are implicated in prostate cancer (PC) progression; however their underlying mechanisms remain elusive. We report that non-canonical activation of estradiol (E2)-ERβ2 signaling axis primes growth, colony-forming ability and migration of the androgen receptor (AR)-null castration-resistant PC (CRPC) cells under androgen-deprived conditions (ADC). The non-classical E2-ERβ2 mediates phosphorylation and activation of Src-IGF-1R complex, which in turn triggers p65-dependent transcriptional upregulation of the androgen-regulated serine protease TMPRSS2:ETV5a/TMPRSS2:ETV5b gene fusions under ADC...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28926939/kempopeptin-c-a-novel-marine-derived-serine-protease-inhibitor-targeting-invasive-breast-cancer
#17
Fatma H Al-Awadhi, Lilibeth A Salvador, Brian K Law, Valerie J Paul, Hendrik Luesch
Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS). The presence of the basic Lys residue adjacent to the N-terminus of the 3-amino-6-hydroxy-2-piperidone (Ahp) moiety contributed to its selectivity towards trypsin and related proteases. The antiproteolytic activity of kempopeptin C was evaluated against trypsin, plasmin and matriptase and found to inhibit these enzymes with IC50 values of 0...
September 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28917266/urinary-biomarkers-in-prostate-cancer-detection-and-monitoring-progression
#18
REVIEW
Duojia Wu, Jie Ni, Julia Beretov, Paul Cozzi, Mark Willcox, Valerie Wasinger, Bradley Walsh, Peter Graham, Yong Li
Prostate cancer (CaP) is the most common cancer in men and the second leading cause of cancer deaths in males in Australia. Although serum prostate-specific antigen (PSA) has been the most widely used biomarker in CaP detection for decades, PSA screening has limitations such as low specificity and potential association with over-diagnosis. Current biomarkers used in the clinic are not useful for the early detection of CaP, or monitoring its progression, and have limited value in predicting response to treatment...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#19
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887309/phosphorylation-of-the-oncogenic-transcription-factor-erg-in-prostate-cells-dissociates-polycomb-repressive-complex-2-allowing-target-gene-activation
#20
Vivekananda Kedage, Brady G Strittmatter, Paige B Dausinas, Peter C Hollenhorst
In ∼50% of prostate cancers, chromosomal rearrangements cause the fusion of the promoter and 5'-UTR of the androgen-regulated TMPRSS2 (transmembrane protease, serine 2) gene to the open reading frame of ERG, encoding an ETS family transcription factor. This fusion results in expression of full-length or N-terminally truncated ERG protein in prostate epithelia. ERG is not expressed in normal prostate epithelia, but when expressed, it promotes tumorigenesis via altered gene expression, stimulating epithelial-mesenchymal transition, cellular migration/invasion, and transformation...
October 20, 2017: Journal of Biological Chemistry
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