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serine protease cancer

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https://www.readbyqxmd.com/read/28526008/cleavage-of-the-urokinase-receptor-upar-on-oral-cancer-cells-regulation-by-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-and-potential-effects-on-migration-and-invasion
#1
Synnove Norvoll Magnussen, Elin Hadler-Olsen, Daniela Elena Costea, Eli Berg, Cristiane Cavalcanti Jacobsen, Bente Mortensen, Tuula Salo, Inigo Martinez-Zubiaurre, Jan-Olof Winberg, Lars Uhlin-Hansen, Gunbjorg Svineng
BACKGROUND: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28522588/a-potential-mechanism-for-adc-induced-neutropenia-role-of-neutrophils-in-their-own-demise
#2
Hui Zhao, Sara Gulesserian, Maria Christina Malinao, Sathish Kumar-Ganesan, James Song, Mi Sook Chang, Melissa M Williams, Zhilan Zeng, Michael Mattie, Brian A Mendelsohn, David R Stover, Fernando Doñate
Neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs) and we aimed to elucidate the potential mechanism of this toxicity. To investigate if ADCs affect neutrophil production from bone marrow, an in vitro assay was developed in which hematopoietic stem cells (HSCs) were differentiated to neutrophils. Several antibodies against targets absent in HSCs and neutrophils were conjugated to MMAE via a cleavable valine-citrulline linker (vcMMAE-ADCs) or MMAF via a non-cleavable maleimidocaproyl linker (mcMMAF-ADCs), and their cytotoxicity was tested in the neutrophil differentiation assay...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521467/upregulation-of-maspin-expression-in-human-cervical-carcinoma-cells-by-transforming-growth-factor-%C3%AE-1-through-the-convergence-of-smad-and-non-smad-signaling-pathways
#3
Ariyaphong Wongnoppavich, Nahathai Dukaew, Sirinthip Choonate, Kongthawat Chairatvit
Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factor β1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28512253/infiltrating-myeloid-cells-exert-pro-tumorigenic-actions-via-neutrophil-elastase
#4
Irina Lerman, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Luis Chiriboga, Chunliu Pan, Kent L Nastiuk, John J Krolewski, Aritro Sen, Stephen R Hammes
Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer (PCa) and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here it is reported that granulocytic myeloid-derived suppressor cells (MDSCs) are the predominant tumor infiltrating cells in PCa xenografts established in athymic nude mice...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28496990/mtorc1-regulates-mannose-6-phosphate-receptor-transport-and-t-cell-vulnerability-to-regulatory-t-cells-by-controlling-kinesin-kif13a
#5
Khawaja Ashfaque Ahmed, Jim Xiang
Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P-bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important role in T-cell activation, migration and contraction. However, molecular mechanisms controlling M6PR expression in T cells remain poorly understood. Here, we show that M6PR expression on T cells is distinctively controlled by two common γ-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR expression is not caused by an altered synthesis of M6PR protein, but is a result of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto cell surfaces...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28466252/tmprss4-upregulates-twist1-expression-through-stat3-activation-to-induce-prostate-cancer-cell-migration
#6
Zhang Jianwei, Li Qi, Xu Quanquan, Wang Tianen, Wang Qingwei
Transmembrane protease serine 4 (TMPRSS4), a type-II transmembrane serine protease, is involved in the development and progression of wide range of tumors. However, the biological role of TMPRSS4 in prostate cancer remains obscure. Here, we investigated the effect of TMPRSS4 on proliferation and migration in prostate cancer and potential mechanisms. Our findings demonstrated over-expression of TMPRSS4 promoted the PC3 prostate cancer cells migration, which could be reversed by TMPRSS4 silencing. TMPRSS4 induced TWIST1 expression and followed progression of EMT along with upregulation of N-cadherin and downregulation of E-cadherin via STAT3 phosphorylation...
May 2, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28460881/rhomboid-proteases-in-human-disease-mechanisms-and-future-prospects
#7
REVIEW
Stefan Düsterhöft, Ulrike Künzel, Matthew Freeman
Rhomboids are intramembrane serine proteases that cleave the transmembrane helices of substrate proteins, typically releasing luminal/extracellular domains from the membrane. They are conserved in all branches of life and there is a growing recognition of their association with a wide range of human diseases. Human rhomboids, for example, have been implicated in cancer, metabolic disease and neurodegeneration, while rhomboids in apicomplexan parasites appear to contribute to their invasion of host cells. Recent advances in our knowledge of the structure and the enzyme function of rhomboids, and increasing efforts to identify specific inhibitors, are beginning to provide important insight into the prospect of rhomboids becoming future therapeutic targets...
April 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28456517/proprotein-convertase-inhibition-paralyzing-the-cell-s-master-switches
#8
Andres J Klein-Szanto, Daniel E Bassi
Proprotein convertases are serine proteases responsible for the cleavage and subsequent activation of protein substrates, many of them relevant for the development of an ample variety of diseases. Seven of the PCs, including furin and PACE4, recognize and hydrolyze the C-terminal end of the general sequence RXRR/KXR, whereas PCSK-9 recognizes a series of non-basic amino acids. In some systems, PC-mediated substrate activation results in the development of pathological processes, such as cancer, endocrinopathies, and cardiovascular and infectious diseases...
April 26, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28454094/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#9
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)...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#10
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28428279/interaction-between-tumor-cell-surface-receptor-rage-and-proteinase-3-mediates-prostate-cancer-metastasis-to-bone
#11
Mikhail G Kolonin, Anna Sergeeva, Daniela I Staquicini, Tracey L Smith, Christy A Tarleton, Jeffrey J Molldrem, Richard L Sidman, Serena Marchiò, Renata Pasqualini, Wadih Arap
Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427756/human-tissue-kallikreins-blood-levels-and-response-to-radiotherapy-in-intermediate-risk-prostate-cancer
#12
Nicola J Nasser, John Thoms, Antoninus Soosaipillai, Melania Pintilie, Ri Wang, Eleftherios P Diamandis, Robert G Bristow
OBJECTIVES: Kallikreins are serine proteases over expressed in many malignancies. In this study, we measure changes in serum kallikrein (KLKs) levels during intensity-modulated radiotherapy (IMRT) in prostate cancer patients, and find potential correlations between serum kallikrein level and normal tissues toxicity during radiation. METHODS: Forty-nine patients with prostate cancer were recruited as follows: group 1, definitive standard fractionation IMRT (78Gy in 39 fractions, n=15); group 2, definitive hypofractionated IMRT (60Gy in 20 fractions, n=15); and group 3, IMRT postprostatectomy (66Gy in 33 fractions, n=19)...
April 17, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28419837/identification-and-molecular-cloning-of-novel-transcripts-of-the-human-kallikrein-related-peptidase-10-klk10-gene-using-next-generation-sequencing
#13
Panagiotis G Adamopoulos, Christos K Kontos, Andreas Scorilas
Tissue kallikrein and kallikrein-related peptidases (KLKs) form the largest group of serine proteases in the human genome, sharing many structural and functional characteristics. Multiple alternative transcripts have been reported for the most human KLK genes, while many of them are aberrantly expressed in various malignancies, thus possessing significant prognostic and/or diagnostic value. Alternative splicing of cancer-related genes is a common cellular mechanism accounting for cancer cell transcriptome complexity, as it affects cell cycle control, proliferation, apoptosis, invasion, and metastasis...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28402938/cathepsins-in-digestive-cancers
#14
REVIEW
Siyuan Chen, Hui Dong, Shiming Yang, Hong Guo
Cathepsins are lysosomal peptidases belonging to the papain family, and based on their catalytic sites, these enzymes can be divided into serine, cysteine and aspartic proteases. The studies conducted to date have identified, 15 types of cathepsins that are widely distributed in intracellular and extracellular spaces. These proteases participate in various pathological activities, including the occurrence and development of human cancers. Several recent studies suggest that cathepsins, particularly cathepsins B, D, E and L, contribute to digestive tumorigenesis...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402100/structural-studies-revealed-active-site-distortions-of-human-furin-by-a-small-molecule-inhibitor
#15
Sven O Dahms, Guan-Sheng Jiao, Manuel E Than
Proprotein convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of several pathologies including cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Here, we present the first experimental complex of furin with a non-substrate-like small molecule inhibitor, and the X-ray structure of the enzyme complexed to the small molecule inhibitor 1 at 1.9 Å resolution. Two molecules of inhibitor 1 were found to interact with furin...
April 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28396256/structural-insights-into-the-activation-mechanisms-of-human-htra-serine-proteases
#16
REVIEW
Dorota Zurawa-Janicka, Tomasz Wenta, Miroslaw Jarzab, Joanna Skorko-Glonek, Przemyslaw Glaza, Artur Gieldon, Jerzy Ciarkowski, Barbara Lipinska
Human HtrA1-4 proteins belong to the HtrA family of evolutionarily conserved serine proteases and function as important modulators of many physiological processes, including maintenance of mitochondrial homeostasis, cell signaling and apoptosis. Disturbances in their action are linked to severe diseases, including oncogenesis and neurodegeneration. The HtrA1-4 proteins share structural and functional features of other members of the HtrA protein family, however there are several significant differences in structural architecture and mechanisms of action which makes each of them unique...
May 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28395722/-inhibitory-effect-and-the-mechanism-of-astragalus-polysaccharide-combined-with-cisplatin-on-growth-of-inplanted-lewis-lung-carcinoma-in-mice
#17
Mengjie Zhuang, Dan Liu, Yanwen Chen, Haixia Ming, Yang Li
Objective To observe the effect of Astragalus polysaccharides (APS) combined with cisplatin (DDP) on the expressions of cytochrome C (CytC) and high temperature required serine protease A2 (Omi/HtrA2) in the mice with Lewis lung carcinoma (LLC) transplantated tumors. Methods Ninty C57BL/6J mice were randomly divided into normal control group, model group, and (50, 100, 200) μg/mL APS groups, 6 mg/kg DDP group, 3 mg/kg DDP combined with (50, 100, 200) μg/mL APS groups. Each group included 10 mice. Except the mice in the normal group, the rest mice were inoculated subcutaneously with LLC cells (1×10(7) mL) at the right fore axillary fossa to establish tumor-bearing mouse models...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28368394/inhibition-of-cyclooxygenase-2-mediated-matriptase-activation-contributes-to-the-suppression-of-prostate-cancer-cell-motility-and-metastasis
#18
C-J Ko, S-W Lan, Y-C Lu, T-S Cheng, P-F Lai, C-H Tsai, T-W Hsu, H-Y Lin, H-Y Shyu, S-R Wu, H-H Lin, P-W Hsiao, C-H Chen, H-P Huang, M-S Lee
Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1β (IL-1β) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28339463/combinations-of-serpinb5-gene-polymorphisms-and-environmental-factors-are-associated-with-oral-cancer-risks
#19
Hsiu-Ting Tsai, Ming-Ju Hsieh, Chiao-Wen Lin, Shih-Chi Su, Nae-Fang Miao, Shun-Fa Yang, Hui-Chuan Huang, Fu-Chih Lai, Yu-Fan Liu
BACKGROUND: We identified rs17071138 T/C, rs3744941 C/T, and rs8089104 T/C gene polymorphisms of SERPINB5 (mammary serine protease inhibitor) that are specific to patients with oral cancer susceptibility and their clinicopathological status. METHODOLOGY/PRINCIPAL FINDINGS: In total, 1342 participants, including 601 healthy controls and 741 patients with oral cancer, were recruited for this study. Allelic discrimination of rs17071138 T/C, rs3744941 C/T, and rs8089104 T/C of the SERPINB5 gene was assessed by a real-time PCR with a TaqMan assay...
2017: PloS One
https://www.readbyqxmd.com/read/28337383/pancreatic-cancer-screening-in-different-risk-individuals-with-family-history-of-pancreatic-cancer-a-prospective-cohort-study-in-taiwan
#20
Ming-Chu Chang, Chih-Horng Wu, Shih-Hung Yang, Po-Chin Liang, Bang-Bin Chen, I-Shiow Jan, Yu-Ting Chang, Yung-Ming Jeng
Pancreatic cancer (PC) is usually diagnosed at advanced stage. Our aim was to investigate the risk of malignant and premalignant pancreatic lesions in individuals with family history of PC. Individuals at risk of PC were enrolled prospectively in a screening program in Taiwan. All risk individuals received genetic testing of cationic trypsinogen (PRSS1) gene and the serine protease inhibitor Kazal type 1 (SPINK1) gene. They were stratified into three risk groups (high, moderate, and low) based on the family history and genetic testing...
2017: American Journal of Cancer Research
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