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https://www.readbyqxmd.com/read/29330435/beta-catenin-cleavage-enhances-transcriptional-activation
#1
Tatiana Goretsky, Emily M Bradford, Qing Ye, Olivia F Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C Keller, Preetika Sinh, Josep M Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A Barrett
Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318553/analyzing-the-type-ii-transmembrane-serine-protease-hepsin-dependent-basement-membrane-remodeling-in-3d-cell-culture
#2
Shishir M Pant, Denis Belitskin, Hanna Ala-Hongisto, Juha Klefström, Topi A Tervonen
Breakdown of the basement membrane is a key step that precedes tumor invasion, and accumulating evidence suggests a key role for the type II transmembrane proteases (TTSPs) in that process. Overexpression of a TTSP hepsin characterizes many solid cancers, including prostate, breast, and ovarian cancer, and in experimental tumor models, the elevated proteolytic activity of hepsin simultaneously activates several growth factors and cleaves basement membrane protein laminin-332, which is an essential component of the cell-basement membrane junction hemidesmosome...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29318543/a-simple-cell-based-assay-for-the%C3%A2-detection-of-surface-protein-shedding-by-rhomboid-proteases
#3
Angela Moncada-Pazos, Adam Graham Grieve
Rhomboids are intramembrane serine proteases that cleave their substrates within or immediately adjacent to their transmembrane domains, a process known as regulated intramembrane proteolysis. In eukaryotes, two main types of rhomboid proteases can be distinguished based on their subcellular localization: mitochondrial rhomboids and secretase-type rhomboids that target the secretory pathway. The latter class can cleave and release the extracellular domain of all epidermal growth factor-like proteins in Drosophila and can liberate epidermal growth factor (EGF) in mammals, in a process known as ectodomain shedding...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29314830/x-ray-structures-of-the-proprotein-convertase-furin-bound-with-substrate-analog-inhibitors-reveal-substrate-specificity-determinants-beyond-the-s4-pocket
#4
Sven O Dahms, Kornelia Hardes, Torsten Steinmetzer, Manuel E Than
The proprotein convertase (PC) furin is a highly specific serine protease modifying and thereby activating proteins in the secretory pathway by proteolytic cleavage. Its substrates are involved in many diseases including cancer and infections caused by bacteria and viruses. Understanding furin's substrate specificity is of crucial importance for the development of pharmacologically applicable inhibitors. Using protein X-ray crystallography we investigated the extended substrate binding site of furin in complex with three peptide derived inhibitors at up to 1...
January 9, 2018: Biochemistry
https://www.readbyqxmd.com/read/29304522/the-pathophysiological-role-of-neutrophil-extracellular-traps-in-inflammatory-diseases
#5
Aldo Bonaventura, Luca Liberale, Federico Carbone, Alessandra Vecchié, Candela Diaz-Cañestro, Giovanni G Camici, Fabrizio Montecucco, Franco Dallegri
Neutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious stimuli. NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29290980/up-regulation-of-5-lipoxygenase-by-inhibition-of-cathepsin-g-enhances-trail-induced-apoptosis-through-down-regulation-of-survivin
#6
Seon Min Woo, Kyoung-Jin Min, Seung Un Seo, Shin Kim, Jong-Wook Park, Dae Kyu Song, Hyun-Shik Lee, Sang Hyun Kim, Taeg Kyu Kwon
Cathepsin G is a serine protease secreted from activated neutrophils, it has important roles in inflammation and immune response. Moreover, cathepsin G promotes tumor cell-cell adhesion and migration in cancer cells. In this study, we investigated whether inhibition of cathepsin G could sensitize TRAIL-mediated apoptosis in cancer cells. An inhibitor of cathepsin G [Cathepsin G inhibitor I (Cat GI); CAS 429676-93-7] markedly induced TRAIL-mediated apoptosis in human renal carcinoma (Caki, ACHN, and A498), lung cancer (A549) and cervical cancer (Hela) cells...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29277318/t2e-tmprss2-erg-fusion-transcripts-are-associated-with-higher-levels-of-amacr-mrna-and-a-subsequent-prostate-cancer-diagnosis-in-patients-with-atypical-small-acinar-proliferation
#7
Isil Ezgi Eryilmaz, Yakup Kordan, Berna Aytac Vuruskan, Onur Kaygısız, Berrin Tunca, Gulsah Cecener
Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 (TMPRSS2) and genes from the ETS transcription factor family, most commonly ERG and ETV1, result in alteration that responsible for oncogenic activity in prostate cancer (PC). The aims of the present study were to: 1) investigate the frequency of these fusion transcripts in prostate tissue samples obtained from patients diagnosed with atypical small acinar proliferation (ASAP), 2) determine any clinical significance of T2E expression at the RNA level in predicting PC detection in subsequent biopsies, and 3) evaluate expression of the PC marker, alpha-methylacyl-CoA racemase (AMACR), according to T2E status by real-time quantitative reverse transcription PCR (RT-qPCR)...
December 22, 2017: Gene
https://www.readbyqxmd.com/read/29273462/fibroblast-activation-proteins-%C3%AE-suppress-tumor-immunity-by-regulating-t-cells-and-tumor-associated-macrophages
#8
Chun Mei Hou, Xue Mei Qu, Jian Zhang, Ting Ting Ding, Wei Han, Guang Chuan Ji, Zhao Hua Zhong, He Chen, Feng-Min Zhang
Fibroblast activation protein-α (FAPα) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in >90% of malignant epithelial carcinomas. FAPα regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment...
December 19, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29250748/age-is-the-work-of-art-impact-of-neutrophil-and-organism-age-on-neutrophil-extracellular-trap-formation
#9
REVIEW
Weronika Ortmann, Elzbieta Kolaczkowska
Neutrophil extracellular traps or NETs are released by highly activated neutrophils in response to infectious agents, sterile inflammation, autoimmune stimuli and cancer. In the cells, the nuclear envelop disintegrates and decondensation of chromatin occurs that depends on peptidylarginine deiminase 4 (PAD4) and neutrophil elastase (NE). Subsequently, proteins from neutrophil granules (e.g., NE, lactoferrin and myeloperoxidase) and the nucleus (histones) bind to decondensed DNA and the whole structure is ejected from the cell...
December 18, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29218249/pericellular-regulation-of-prostate-cancer-expressed-kallikrein-related-peptidases-and-matrix-metalloproteinases-by-cell-surface-serine-proteases
#10
Janet C Reid, Admire Matsika, Claire M Davies, Yaowu He, Amy Broomfield, Nigel C Bennett, Viktor Magdolen, Bhuvana Srinivasan, Judith A Clements, John D Hooper
We provide evidence of a pericellular network of proteases that are elevated and co-expressed in prostate cancer. The network involves the membrane bound serine proteases hepsin and TMPRSS2, the secreted kallikrein-related peptidases KLK4 and KLK14, and the secreted matrix metalloproteinases MMP-3 and MMP-9. Western blot analysis of cell lysates, conditioned cell culture media, immunoprecipitates and cell surface proteins, demonstrates a network of interactions centred largely at the plasma membrane, with the Arg/Lys specific proteases hepsin and TMPRSS2 key regulators of the network...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29207091/fibroblast-activation-protein-%C3%AE-in-tumor-cells-promotes-colorectal-cancer-angiogenesis-via-the-akt-and-erk-signaling-pathways
#11
Feng Cao, Songsong Wang, Huanqin Wang, Wei Tang
Fibroblast activation protein-α (FAP-α) is a cell surface serine protease of the post-prolyl peptidase family, and stromal FAP-α expression may serve important functions in tumor occurrence and progression. In recent years, FAP-α expression in tumor cells has been detected in a number of types of tumor, and its roles in tumor growth and metastasis have been reported. However, the presence of FAP-α in colorectal cancer (CRC) cells lacks sufficient evidence and its role in angiogenesis remains unknown. The present study confirmed FAP-α expression in CRC cells at the tissue and cellular level, using immunohistochemistry and western blot analysis, respectively; it additionally identified that FAP-α in CRC cells was positively associated with vascular endothelial growth factor (VEGF)-A expression and microvessel density in stained tissue samples for the first time...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206443/site-specific-64cu-labelling-of-the-serine-protease-active-site-inhibited-factor-seven-azide-fviiai-n3-using-copper-free-click-chemistry
#12
Troels Elmer Jeppesen, Lotte Kellemann Kristensen, Carsten Haagen Nielsen, Lars Christian Petersen, Jesper Bøggild Kristensen, Carsten Behrens, Jacob Madsen, Andreas Kjær
A method for site-specific radiolabelling of the serine protease active site inhibited factor seven (FVIIai) with 64Cu has been applied using a biorthogonal click reaction. FVIIai binds to tissue factor (TF), a trans-membrane protein involved involved in haemostasis, angiogenesis, proliferation, cell migration, and survival of cancer cells. First a single azide moiety was introduced in the active site of this 50 kDa protease. Then a NOTA moiety was introduced via a strain promoted azide-alkyne reaction and the corresponding conjugate was labelled with 64Cu...
December 5, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29202869/prognostic-significance-of-hepatocyte-growth-factor-activator-inhibitor-type-1-hai-1-immunoreactivity-in-pancreatic-ductal-adenocarcinoma
#13
Chihiro Sakugawa, Yukihiro Haruyama, Hiroyuki Tanaka, Tsuyoshi Fukushima, Makiko Kawaguchi, Hiroaki Kataoka
OBJECTIVE: Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor that is expressed on the surface of epithelial cells. Evidence has suggested that decreased cell surface HAI-1 in carcinoma cells results in enhanced invasiveness. However, little is known regarding the expression of HAI-1 in pancreatic ductal adenocarcinoma (PDAC). This study aimed to analyze HAI-1 expression in PDAC and its impact on patient prognosis. RESULTS: HAI-1 immunohistochemistry was performed on samples from 67 PDAC cases...
December 4, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29196918/nafamostat-mesilate-negatively-regulates-the-metastasis-of-triple-negative-breast-cancer-cells
#14
Sunam Mander, Dong-Joo You, Sumi Park, Dong Hwi Kim, Hyo Jeong Yong, Dong-Sik Kim, Curie Ahn, Yun-Hee Kim, Jae Young Seong, Jong-Ik Hwang
Triple-negative breast cancer (TNBC) lacking of oestrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2 is a highly malignant disease which results in a poor prognosis and rare treatment options. Despite the use of conventional chemotherapy for TNBC tumours, resistance and short duration responses limit the treatment efficacy. Therefore, a need exists to develop a new chemotherapy for TNBC. The aim of this study was to examine the anti-cancer effects of nafamostat mesilate (NM), a previously known serine protease inhibitor and highly safe drug on breast cancer cells...
December 1, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29192477/mast-cells-and-cancer-a-review-of-literature
#15
Giovanni Paolino, Paola Corsetti, Elisa Moliterni, Serena Corsetti, Dario Didona, Marcello Albanesi, Carlo Mattozzi, Paolo Lido, Stefano Calvieri
Mast cells (MCs) are a potent proangiogenic factor in tumors, they product several pro- angiogenic factors such as fibroblast growth factor 2 (FGF-2), vascular epithelial growth factor (VEGF), tryptase and chymase. Tryptase is a serine protease classified as α-tryptase and β-tryptase, both produced by MCs. Tryptase degrades the tissues, playing an important role in angiogenesis and in the development of metastases. Serum tryptase increases with age, with increased damage to cells and risk of developing a malignancy and it could be considered the expression of a fundamental role of MCs in tumor growth or, on the contrary, in the antitumor response...
November 30, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/29187436/identification-of-cpg-sites-of-serpina5-promoter-with-opposite-methylation-patterns-in-benign-and-malignant-prostate-cells
#16
Albert Hagelgans, Carsten Jandeck, Markus Friedemann, Anastasia Donchin, Susan Richter, Mario Menschikowski
BACKGROUND/AIM: To date there has been no investigation into the epigenetic regulation of the serine protease inhibitor SERPINA5 in prostate cancer, where lack of this gene was considered to facilitate invasive growth patterns. MATERIALS AND METHODS: Methylation degrees of eight CpG sites of SERPINA5 were analyzed in normal and malignant prostate cells using nucleotide sequencing, methylation-specific high resolution melting and digital droplet PCR techniques. RESULTS: The methylation degree of five CpG sites significantly correlated with lower SERPINA5 expression levels...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29168038/ovarian-serous-carcinomas-acquire-cisplatin-resistance-and-increased-invasion-through-downregulation-of-the-high-temperature-required-protein-a2-htra2-following-repeated-treatment-with-cisplatin
#17
Hiroaki Soyama, Morikazu Miyamoto, Masashi Takano, Tadashi Aoyama, Hiroko Matsuura, Takahiro Sakamoto, Kazuki Takasaki, Mika Kuwahara, Kento Kato, Tomoyuki Yoshikawa, Hideki Iwahashi, Hitoshi Tsuda, Kenichi Furuya
High-temperature-required protein A2 (HtrA2) is one of the serine proteases related to apoptosis. HtrA2 protein expression has been associated with cisplatin resistance and poor prognosis in ovarian serous adenocarcinoma (SAC). The aim of this study was to understand the influence of HtrA2 on repeated treatment with cisplatin. The change in HtrA2 expression in 31 ovarian cancers was investigated by immunohistochemical analysis, before and after cisplatin-based chemotherapy, and the association between HtrA2 expression after chemotherapy and prognosis was analyzed...
November 22, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29133591/chemokine-signaling-facilitates-early-stage-breast-cancer-survival-and-invasion-through-fibroblast-dependent-mechanisms
#18
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
#19
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
#20
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
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