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https://www.readbyqxmd.com/read/27915333/prss8-is-downregulated-and-suppresses-tumour-growth-and-metastases-in-hepatocellular-carcinoma
#1
Li Zhang, Guozhan Jia, Binya Shi, Guanqun Ge, Hongbin Duan, Yunsheng Yang
BACKGROUND: Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC). METHODS: PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed...
December 5, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27755216/altered-prostasin-cap1-prss8-expression-favors-inflammation-and-tissue-remodeling-in-dss-induced-colitis
#2
Anna Keppner, Sumedha Malsure, Antoine Nobile, Muriel Auberson, Olivier Bonny, Edith Hummler
BACKGROUND: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)-induced colitis. METHODS: Wildtype, heterozygous (fr/+), and homozygous (fr/fr) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression...
October 12, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27385010/delineation-of-proteolytic-and-non-proteolytic-functions-of-the-membrane-anchored-serine-protease-prostasin
#3
Roman Szabo, Taliya Lantsman, Diane E Peters, Thomas H Bugge
The membrane-anchored serine proteases prostasin (PRSS8) and matriptase (ST14) initiate a cell surface proteolytic pathway essential for epithelial function. Mice expressing only catalytically inactive prostasin are viable, unlike prostasin null mice, indicating that at least some prostasin functions are non-proteolytic. Here we used knock-in mice expressing catalytically inactive prostasin (Prss8(Ki/Ki)) to show that the physiological and pathological functions of prostasin vary in their dependence on its catalytic activity...
August 1, 2016: Development
https://www.readbyqxmd.com/read/27081034/prss8-methylation-and-its-significance-in-esophageal-squamous-cell-carcinoma
#4
Yonghua Bao, Qian Wang, Yongchen Guo, Zhiguo Chen, Kai Li, Yiqiong Yang, Huijuan Zhang, Huali Dong, Kui Shen, Wancai Yang
Esophageal cancer is one of the most common cancers worldwide, and the incidence and mortality is increasing rapidly in recent years in China, but the underlying mechanisms are largely unclear. Herein we found that the expression of PRSS8, a serine protease prostasin, is significantly decreased in esophageal squamous cell carcinomas (ESCC) at mRNA and protein levels. The reduction of PRSS8 was well correlated with poor differentiation and shorter survival time. Interestingly, ESCC stromal expression of PRSS8 was significantly correlated with stromal lymphocyte infiltration and cancer progression...
May 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27050145/tumor-suppressor-prss8-targets-sphk1-s1p-stat3-akt-signaling-in-colorectal-cancer
#5
Yonghua Bao, Kai Li, Yongchen Guo, Qian Wang, Zexin Li, Yiqiong Yang, Zhiguo Chen, Jianguo Wang, Weixing Zhao, Huijuan Zhang, Jiwang Chen, Huali Dong, Kui Shen, Alan M Diamond, Wancai Yang
PRSS8 is a membrane-anchored serine protease prostasin and has been shown an association with carcinogenesis. Herein we found that PRSS8 expression was significantly reduced in colorectal adenomas and adenocarcinomas. The decreased PRSS8 was well correlated with clinical stages, poor differentiation and shorter survival time of colorectal cancer. Furthermore, increase of PRSS8 led to the inhibition of colorectal cancer cell proliferation, knockdown of PRSS8 accelerated cell proliferation in vitro, and overexpressing PRSS8 retarded cancer cell growth in nude mice...
May 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27036110/the-serine-protease-prostasin-prss8-is-a-potential-biomarker-for-early-detection-of-ovarian-cancer
#6
Ayala Tamir, Anju Gangadharan, Sakshi Balwani, Takemi Tanaka, Ushma Patel, Ahmed Hassan, Stephanie Benke, Agnieszka Agas, Joseph D'Agostino, Dayoung Shin, Sunghoon Yoon, Andre Goy, Andrew Pecora, K Stephen Suh
BACKGROUND: Ovarian cancer (OVC) is the deadliest of all gynecologic cancers, primarily as a consequence of asymptomatic progression. The complex nature of OVC creates challenges for early detection, and there is a lack of specific and sensitive biomarkers suitable for screening and detecting early stage OVC. METHODS: Potential OVC biomarkers were identified by bioinformatic analysis. Candidates were further screened for differential expression in a library of OVC cell lines...
2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/26102680/8c-02-the-serine-protease-prostasin-is-aberrantly-filtrated-in-urine-in-preeclampsia-with-similar-levels-in-plasma-and-placenta-tissue-compared-to-normal-pregnancy
#7
B L Jensen, B Frederiksen-Moller, J S Jorgensen, L Vogel, O Krigslund, L B Andersen
OBJECTIVE: The serine protease prostasin (PRSS8, CAP1) and its activator matriptase and inhibitor nexin-1 are necessary for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension. It was hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomeular barrier...
June 2015: Journal of Hypertension
https://www.readbyqxmd.com/read/25812384/-prostasin-prss8-as-a-new-pathological-factor
#8
REVIEW
Kohei Uchimura, Kenichiro Kitamura
Serine proteases play pivotal roles in many biological processes including clotting, digestion, and immune system. A glycosylphosphatidylinositol-anchored serine protease prostasin(PRSS8) is ubiquitously expressed in many tissues such as kidney, prostate, skin, liver, lung, and colon. However, the physiological role for PRSS8 has not been fully understood. Recently, we have identified a novel role for PRSS8 in the regulation of glucose homeostasis via Toll-like receptor 4(TLR4)-mediated signaling in the liver and demonstrated new insight into the development of diabetes resulting from obesity-induced inflammation or metabolic endotoxemia...
March 2015: Nihon Rinsho. Japanese Journal of Clinical Medicine
https://www.readbyqxmd.com/read/25787629/-280-pos-prostasin-and-its-regulatory-proteins-in-human-placentas-from-pregnant-women-with-preeclampsia-and-healthy-pregnant-controls
#9
Britta Frederiksen-Møller, Jan Stener Jørgensen, Lotte Katrine Vogel, Boye Lagerbon Jensen
OBJECTIVES: Serine proteases are enzymes involved in digestion, immune response, blood coagulation and reproduction. The serine protease prostasin (PRSS8, CAP1) and its regulatory associated proteins (Matriptase, Hepatocyt growth factor activator inhibitors (HAIs), and Nexin-1) are essential for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension...
January 2015: Pregnancy Hypertension
https://www.readbyqxmd.com/read/25753662/an-intrinsically-disordered-region-of-methyl-cpg-binding-domain-protein-2-mbd2-recruits-the-histone-deacetylase-core-of-the-nurd-complex
#10
Megha A Desai, Heather D Webb, Leander M Sinanan, J Neel Scarsdale, Ninad M Walavalkar, Gordon D Ginder, David C Williams
The MBD2-NuRD (Nucleosome Remodeling and Deacetylase) complex is an epigenetic reader of DNA methylation that regulates genes involved in normal development and neoplastic diseases. To delineate the architecture and functional interactions of the MBD2-NuRD complex, we previously solved the structures of MBD2 bound to methylated DNA and a coiled-coil interaction between MBD2 and p66α that recruits the CHD4 nucleosome remodeling protein to the complex. The work presented here identifies novel structural and functional features of a previously uncharacterized domain of MBD2 (MBD2IDR)...
March 31, 2015: Nucleic Acids Research
https://www.readbyqxmd.com/read/25138159/the-cap1-prss8-catalytic-triad-is-not-involved-in-par2-activation-and-protease-nexin-1-pn-1-inhibition
#11
Giovanna Crisante, Laura Battista, Justyna Iwaszkiewicz, Valeria Nesca, Anne-Marie Mérillat, Chloé Sergi, Vincent Zoete, Simona Frateschi, Edith Hummler
Serine proteases, serine protease inhibitors, and protease-activated receptors (PARs) are responsible for several human skin disorders characterized by impaired epidermal permeability barrier function, desquamation, and inflammation. In this study, we addressed the consequences of a catalytically dead serine protease on epidermal homeostasis, the activation of PAR2 and the inhibition by the serine protease inhibitor nexin-1. The catalytically inactive serine protease CAP1/Prss8, when ectopically expressed in the mouse, retained the ability to induce skin disorders as well as its catalytically active counterpart (75%, n=81)...
November 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/24940735/gene-expression-correlations-in-human-cancer-cell-lines-define-molecular-interaction-networks-for-epithelial-phenotype
#12
Kurt W Kohn, Barry M Zeeberg, William C Reinhold, Yves Pommier
Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute's CCLE cell lines...
2014: PloS One
https://www.readbyqxmd.com/read/24706745/the-membrane-anchored-serine-protease-prostasin-cap1-prss8-supports-epidermal-development-and-postnatal-homeostasis-independent-of-its-enzymatic-activity
#13
Diane E Peters, Roman Szabo, Stine Friis, Natalia A Shylo, Katiuchia Uzzun Sales, Kenn Holmbeck, Thomas H Bugge
The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. Prostasin null (Prss8(-/-)) mice lack barrier formation and display fatal postnatal dehydration. In sharp contrast, mice homozygous for a point mutation in the Prss8 gene, which causes the substitution of the active site serine within the catalytic histidine-aspartate-serine triad with alanine and renders prostasin catalytically inactive (Prss8(Cat-/Cat-) mice), develop barrier function and are healthy when followed for up to 20 weeks...
May 23, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24614850/the-serine-protease-prostasin-regulates-hepatic-insulin-sensitivity-by-modulating-tlr4-signalling
#14
Kohei Uchimura, Manabu Hayata, Teruhiko Mizumoto, Yoshikazu Miyasato, Yutaka Kakizoe, Jun Morinaga, Tomoaki Onoue, Rika Yamazoe, Miki Ueda, Masataka Adachi, Taku Miyoshi, Naoki Shiraishi, Wataru Ogawa, Kazuki Fukuda, Tatsuya Kondo, Takeshi Matsumura, Eiichi Araki, Kimio Tomita, Kenichiro Kitamura
The effects of high-fat diet (HFD) and postprandial endotoxemia on the development of type 2 diabetes are not fully understood. Here we show that the serine protease prostasin (PRSS8) regulates hepatic insulin sensitivity by modulating Toll-like receptor 4 (TLR4)-mediated signalling. HFD triggers the suppression of PRSS8 expression by inducing endoplasmic reticulum (ER) stress and increases the TLR4 level in the liver. PRSS8 releases the ectodomain of TLR4 by cleaving it, which results in a reduction in the full-length form and reduces the activation of TLR4...
2014: Nature Communications
https://www.readbyqxmd.com/read/24480829/colon-specific-deletion-of-epithelial-sodium-channel-causes-sodium-loss-and-aldosterone-resistance
#15
Sumedha Malsure, Qing Wang, Roch-Philippe Charles, Chloe Sergi, Romain Perrier, Birgitte Mønster Christensen, Marc Maillard, Bernard C Rossier, Edith Hummler
Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet...
July 2014: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/23724145/long-term-exposure-to-cigarette-smoke-extract-induces-hypomethylation-at-the-runx3-and-igf2-h19-loci-in-immortalized-human-urothelial-cells
#16
Li-Mei Chen, Jennifer C Nergard, Liqiang Ni, Charles J Rosser, Karl X Chai
Cigarette smoking is the single most important epidemiological risk factor for bladder cancer but it is not known whether exposure of urothelial cells to the systemic soluble contents of cigarette smoke is directly causative to bladder cancer and the associated epigenetic changes such as tumor suppressor gene hypermethylation. We undertook this study to investigate if long-term treatment of human urothelial cells with cigarette smoke extract (CSE) results in tumor suppressor gene hypermethylation, a phenotype that was previously associated with long-term constant CSE treatment of airway epithelial cells...
2013: PloS One
https://www.readbyqxmd.com/read/23405214/the-channel-activating-protease-cap1-prss8-is-required-for-placental-labyrinth-maturation
#17
Edith Hummler, Aline Dousse, Audrey Rieder, Jean-Christophe Stehle, Isabelle Rubera, Maria-Chiara Osterheld, Friedrich Beermann, Simona Frateschi, Roch-Philippe Charles
The serine protease CAP1/Prss8 is crucial for skin barrier function, lung alveolar fluid clearance and has been unveiled as diagnostic marker for specific cancer types. Here, we show that a constitutive knockout of CAP1/Prss8 leads to embryonic lethality. These embryos presented no specific defects, but it is during this period, and in particular at E13.5, that wildtype placentas show an increased expression of CAP1/Prss8, thus suggesting a placental defect in the knockout situation. The placentas of knockout embryos exhibited significantly reduced vascular development and incomplete cellular maturation...
2013: PloS One
https://www.readbyqxmd.com/read/23319948/early-detection-biomarkers-for-ovarian-cancer
#18
Sreeja Sarojini, Ayala Tamir, Heejin Lim, Shihong Li, Shifang Zhang, Andre Goy, Andrew Pecora, K Stephen Suh
Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both...
2012: Journal of Oncology
https://www.readbyqxmd.com/read/23285254/positive-selection-in-the-chromosome-16-vkorc1-genomic-region-has-contributed-to-the-variability-of-anticoagulant-response-in-humans
#19
Blandine Patillon, Pierre Luisi, Hélène Blanché, Etienne Patin, Howard M Cann, Emmanuelle Génin, Audrey Sabbagh
VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2) is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK). This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus...
2012: PloS One
https://www.readbyqxmd.com/read/22969854/development-of-a-survival-prediction-model-for-gastric-cancer-using-serine-proteases-and-their-inhibitors
#20
Ke-Feng Lei, Bing-Ya Liu, Xiao-Qing Zhang, Xiao-Long Jin, Yan Guo, Min Ye, Zheng-Gang Zhu
Proteolytic enzymes play a key role in the metastatic stage of gastric cancer (GC). In this study, we aimed to identify the serine proteases (SPs) and their inhibitors (serpins) as related to GC. The gene expression profiles of 40 cases of GC were initially detected by cDNA microarray. The results of the differentially expressed SPs and their inhibitor genes from the microarrays were confirmed by real-time PCR. The status of the immunohistochemical staining of the confirmed genes in patients with complete data was used to develop a survival prediction model...
January 2012: Experimental and Therapeutic Medicine
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