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https://www.readbyqxmd.com/read/29622675/sorting-nexin-9-snx9-regulates-levels-of-the-transmembrane-disintegrin-and-metalloproteinase-adam-9-at-the-cell-surface
#1
Kasper Johansen Mygind, Theresa Störiko, Marie L Freiberg, Jacob Samsøe-Petersen, Jeanette Schwarz, Olav M Andersen, Marie Kveiborg
ADAM9 is an active member of the family of transmembrane a disintegrin and metalloproteases (ADAMs). It plays a role in processes such as bone formation and retinal neovascularization, and importantly, its expression in human cancers correlates with disease stage and poor prognosis. Functionally, ADAM9 can cleave several transmembrane proteins, thereby shedding their ectodomains from the cell surface. Moreover, ADAM9 regulates cell behaviour by binding cell-surface receptors such as integrin and membrane-type matrix metalloproteases...
April 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29550974/the-pleiotropic-roles-of-adam9-in-the-biology-of-solid-tumors
#2
REVIEW
Victor O Oria, Paul Lopatta, Oliver Schilling
A disintegrin and a metalloprotease (ADAM) 9 is a metzincin cell-surface protease involved in several biological processes such as myogenesis, fertilization, cell migration, inflammatory response, proliferation, and cell-cell interactions. ADAM9 has been found over-expressed in several solid tumors entities such as glioma, melanoma, prostate cancer, pancreatic ductal adenocarcinoma, gastric, breast, lung, and liver cancers. Immunohistochemical analyses highlight ADAM9 expression by actual cancer cells and associate its abundant presence with clinicopathological features such as shortened overall survival, poor tumor grade, de-differentiation, therapy resistance, and metastasis formation...
March 17, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29434796/adam-proteases-involved-in-inflammation-are-differentially-altered-in-patients-with-gastritis-or-ulcer
#3
Nuray Erin, Sema Türker, Özlem Elpek, Bülent Yildirim
ADAM metallopeptidase domain (ADAM)9, 10 and 17 have α-secretase activity that regulates ectodomain shedding of factors involved in inflammation, cell proliferation, angiogenesis, and wound healing. The secretase activity of ADAM proteins is known to induce an inflammatory response. However, under certain conditions, a lack of secretase activity may induce inflammation suggesting differential roles of ADAM proteins with secretase activity. To the best of our knowledge, the present study evaluated the changes in α-secretase activity and expression of associated ADAM proteases (ADAM9, 10 and 17) in the gastric mucosa of patients with gastritis and ulcers, for the first time...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432845/adam9-mediates-the-interleukin-6-induced-epithelial-mesenchymal-transition-and-metastasis-through-ros-production-in-hepatoma-cells
#4
Yinying Dong, Zhifeng Wu, Mingyan He, Yuhan Chen, Yixing Chen, Xiaoyun Shen, Xiaomei Zhao, Li Zhang, Baoying Yuan, Zhaochong Zeng
Interleukin (IL)-6 has been implicated in the invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular events that mediate this process are poorly understood. Here, we showed that IL-6 promoted the epithelial-mesenchymal transition (EMT) in HCC cell lines, and upregulated a disintegrin and metalloprotease 9 (ADAM9) expression by activating the JNK signaling pathway. ADAM9 was upregulated in human HCCs which promoted HCC cell invasion and the EMT by interacting with NADPH oxidase 1 and inducing reactive oxygen species generation...
May 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29416721/collagen-xvii-laminin-5-activates-epithelial-to-mesenchymal-transition-and-is-associated-with-poor-prognosis-in-lung-cancer
#5
Chen-Chi Liu, Jiun-Han Lin, Tien-Wei Hsu, Jyuan-Wei Hsu, Jer-Wei Chang, Kelly Su, Han-Shui Hsu, Shih-Chieh Hung
Epithelial-to-mesenchymal transition (EMT) is associated with tumor metastasis and tumorigenesis in lung cancer stem-like cells (CSCs). However, the exact mechanism underlying this is not clear. We used microarray analysis to identify candidate genes responsible for EMT in spheroid and monolayer cultures of lung cancer cells. We found increased expression of a variety of adhesion molecules in CSCs. One of these molecules, Collagen XVII (Col XVII), was demonstrated to be required for maintenance of EMT phenotypes and metastasis ability in lung CSCs...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29285199/overexpression-of-adam9-in-oral-squamous-cell-carcinoma
#6
Pattaramon Tanasubsinn, Win Pa Pa Aung, Supansa Pata, Witida Laopajon, Anupong Makeudom, Thanapat Sastraruji, Watchara Kasinrerk, Suttichai Krisanaprakornkit
Overexpression of a disintegrin and metalloproteinase 9 (ADAM9) has been shown in various types of cancer. Some studies have reported inconclusive findings regarding chromosomal aberrations in the ADAM9 -containing region and ADAM9 expression in oral cancer. Therefore, in this study, ADAM9 protein expression was determined and compared between oral squamous cell carcinoma (OSCC) and normal oral tissues, and between oral cancer cell lines and human oral keratinocytes (HOKs). In total, 34 OSCC and 10 healthy paraffin-embedded tissue sections were probed with an anti-ADAM9 antibody, and the immunohistochemical score was determined by multiplying the percentage of positively stained cells with the intensity score...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29247567/adam9-is-over-expressed-in-human-ovarian-clear-cell-carcinomas-and-suppresses-cisplatin-induced-cell-death
#7
Mari Ueno, Takayuki Shiomi, Satsuki Mochizuki, Miyuki Chijiiwa, Masayuki Shimoda, Yae Kanai, Fumio Kataoka, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki, Yasunori Okada
ADAMs (a disintegrin and metalloproteinases) are involved in various biological events such as cell adhesion, migration and invasion, membrane protein shedding and proteolysis. However, there have been no systematic studies on the expression of ADAMs in human ovarian carcinomas. We therefore examined mRNA expression of all the proteolytic ADAM species including ADAM8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30, 33 and ADAMDEC1 in human ovarian carcinomas, and found that prototype membrane-anchored ADAM9m, but not secreted isoform ADAM9s, is significantly over-expressed in carcinomas than in control non-neoplastic ovarian tissue...
February 2018: Cancer Science
https://www.readbyqxmd.com/read/29203614/copy-number-profiling-of-oncogenes-in-ductal-carcinoma-in-situ-of-the-male-breast
#8
Marijn A Vermeulen, Shusma C Doebar, Carolien H M van Deurzen, John W M Martens, Paul J van Diest, Cathy B Moelans
Characterizing male breast cancer (BC) and unraveling male breast carcinogenesis is challenging because of the rarity of this disease. We investigated copy number status of 22 BC-related genes in 18 cases of pure ductal carcinoma in situ (DCIS) and in 49 cases of invasive carcinoma (IC) with adjacent DCIS (DCIS-AIC) in males using multiplex ligation-dependent probe amplification (MLPA). Results were compared to female BC and correlated with survival. Overall, copy number ratio and aberration frequency including all 22 genes showed no significant difference between the 3 groups...
March 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29163713/microrna-154-adam9-axis-inhibits-the-proliferation-migration-and-invasion-of-breast-cancer-cells
#9
Chengwei Qin, Yanming Zhao, Chunzhi Gong, Zhenlin Yang
Breast cancer is the leading cause for cancer-associated mortality in women. Although great progress has been made in the earlier diagnosis and systemic therapy of patients with breast cancer in recent years, recurrence or distant metastasis continue to present major barriers to the successful treatment of breast cancer. Therefore, fully understanding the molecular mechanisms underlying the progression of breast cancer may be critical for the development of effective therapeutic strategies against breast cancer...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142101/loss-of-adam9-expression-impairs-%C3%AE-1-integrin-endocytosis-focal-adhesion-formation-and-cancer-cell-migration
#10
Kasper J Mygind, Jeanette Schwarz, Pranshu Sahgal, Johanna Ivaska, Marie Kveiborg
The transmembrane protease ADAM9 is frequently upregulated in human cancers, and it promotes tumour progression in mice. In vitro , ADAM9 regulates cancer cell adhesion and migration by interacting with integrins. However, how ADAM9 modulates integrin functions is not known. We here show that ADAM9 knockdown increases β1 integrin levels through mechanisms that are independent of its protease activity. In ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins...
January 4, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29119055/mir-488-suppresses-cell-proliferation-and-invasion-by-targeting-adam9-and-lncrna-hulc-in-hepatocellular-carcinoma
#11
Dengdi Hu, Dan Shen, Min Zhang, Nengmeng Jiang, Feng Sun, Shibo Yuan, Kaiming Wan
MicroRNAs (miRNAs) have been identified as regulators of tumor proliferation, invasion, and metastasis in hepatocellular carcinoma (HCC). In the current study, we determined the clinical significance and biological role of miR-488 in HCC. Our results demonstrated that the expression of miR-488 was notably downregulated in HCC tissues compared with paired adjacent normal tissues. Lower miR-488 expression was positively associated with tumor size, vascular invasion, and shorter overall survival (OS) in HCC patients...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29118335/adam9-promotes-lung-cancer-progression-through-vascular-remodeling-by-vegfa-angpt2-and-plat
#12
Chen-Yuan Lin, Chia-Fong Cho, Shih-Ting Bai, Jing-Pei Liu, Ting-Ting Kuo, Li-Ju Wang, Yu-Sen Lin, Ching-Chan Lin, Liang-Chuan Lai, Tzu-Pin Lu, Chih-Ying Hsieh, Chin-Nan Chu, Da-Chuan Cheng, Yuh-Pyng Sher
Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115634/galangin-increases-erk1-2-phosphorylation-to-decrease-adam9-expression-and-prevents-invasion-in-a172-glioma-cells
#13
Deqiang Lei, Fangcheng Zhang, Dongxiao Yao, Nanxiang Xiong, Xiaobing Jiang, Hongyang Zhao
Galangin (3,5,7‑trihydroxyflavone), is a natural flavonoid present in plants. Galangin is reported to exhibit anti‑cancer properties against various cancer types. The aim of the present study was to display the effects of galangin on glioma and its mechanism of action in A172 human glioma cancer cells. The results clearly indicated that treatment of galangin inhibited A172 cell migration and invasion under non‑toxic doses. A human proteinase array assay was conducted to elucidate the potential effects of galangin, and the obtained results demonstrated that treatment of galangin inhibited ADAM9 protein expression and mRNA expression, that are known to contribute to cancer progression...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29055152/predominance-of-regorafenib-over-sorafenib-restoration-of-membrane-bound-mica-in-hepatocellular-carcinoma-cells
#14
Jun Arai, Kaku Goto, Anthony Stephanou, Yasushi Tanoue, Sayaka Ito, Ryosuke Muroyama, Yasuo Matsubara, Ryo Nakagawa, Sayuri Morimoto, Yoshimi Kaise, Lay Ahyoung Lim, Hitoshi Yoshida, Naoya Kato
BACKGROUND AND AIM: The multi-kinase inhibitor regorafenib (REG) was recently demonstrated to be effective in patients with sorafenib (SOR)-resistant hepatocellular carcinoma (HCC). Interestingly, SOR is known to enhance the accumulation of membrane-bound MHC class I polypeptide-related sequence A (mMICA) in HCC cells, and to block production of soluble MICA (sMICA), an immunological decoy. In addition, MICA is associated with HCC in patients with chronic hepatitis C. We have now compared the impact of REG and SOR on MICA in HCC cells, as well as the immunotherapeutic implications thereof...
October 21, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28961505/hyperforin-attenuates-aluminum-induced-a%C3%AE-production-and-tau-phosphorylation-via-regulating-akt-gsk-3%C3%AE-signaling-pathway-in-pc12-cells
#15
Wanyue Huang, Ping Cheng, Kaiyuan Yu, Yanfei Han, Miao Song, Yanfei Li
Aluminum (Al) is a neurotoxicant and cause β-amyloid (Aβ) peptides aggregation and tau hyperphosphorylation. Hyperforin (HF) is one of the major active constituents of the extracts of St. John's Wort (Hypericum perforatum), can treat Alzheimer's disease (AD) and other diseases involving peptide accumulation and cognition impairment. To determine the effects of HF on Al-induced Aβ formation and tau hyperphosphorylation, PC12 cells were cultured and treated with Al-malt (500μM) and/or HF (1μM). The results showed that HF treatment significantly attenuated Al-malt-induced Aβ1-42 production by reducing the expressions of APP, BACE1 and PS1, while increasing the expressions of sAPPα, ADAM9/10/17, and tau phosphorylation in PC12 cells...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28928095/adam9-is-present-at-endothelial-cell-cell-junctions-and-regulates-monocyte-endothelial-transmigration
#16
William R English, Richard J Siviter, Martin Hansen, Gillian Murphy
We have found that A Disintegrin And Metalloproteinase-9 (ADAM9) localises to cell-cell junctions with VE-Cadherin in confluent endothelial monolayers. Co-cultures of cells separately transfected with ADAM9-EGFP or ADAM9-HA showed expression is required in two adjacent cells for localisation to cell-cell junctions suggesting the ADAM9 ectodomain may self-associate. A direct interaction between ADAM9 ectodomains was confirmed using recombinant proteins and an ELISA based method. As the ADAM9 ectodomain can also exist as a soluble form physiologically, we examined if this could inhibit endothelial functions dependent on cell-cell junctions...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28762604/tmeff2-shedding-is-regulated-by-oxidative-stress-and-mediated-by-adams-and-transmembrane-serine-proteases-implicated-in-prostate-cancer
#17
Katarzyna Gaweł-Bęben, Nazim Ali, Vincent Ellis, Gloria Velasco, Zaruhi Poghosyan, Ann Ager, Vera Knäuper
TMEFF2 is a type I transmembrane protein with two follistatin (FS) and one EGF-like domain over-expressed in prostate cancer; however its biological role in prostate cancer development and progression remains unclear, which may, at least in part, be explained by its proteolytic processing. The extracellular part of TMEFF2 (TMEFF2-ECD) is cleaved by ADAM17 and the membrane-retained fragment is further processed by the gamma-secretase complex. TMEFF2 shedding is increased with cell crowding, a condition associated with the tumour microenvironment, which was mediated by oxidative stress signalling, requiring jun-kinase (JNK) activation...
August 1, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28713950/microrna%C3%A2-302a-suppresses-cell-proliferation-migration-and-invasion-in-osteosarcoma-by-targeting-adam9
#18
Xiaoming Yang, Yan Cui, Fuqiang Yang, Chao Sun, Xuejian Gao
Osteosarcoma (OS) is the most frequent malignant primary bone tumor arising from primitive bone‑forming mesenchymal cells in children and adolescents. The dysregulation of microRNAs (miRNAs) has been reported in OS, and these aberrantly expressed miRNAs are involved in the initiation and progression of OS. The aim of the present study was to investigate the expression and functions of miRNA‑302a (miR‑302a) in OS and its underlying mechanism. It was found that the expression of miR‑302a was reduced in OS tissues and cell lines...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28675123/adam9-expression-promotes-an-aggressive-lung-adenocarcinoma-phenotype
#19
Céline Mongaret Kossmann, Maxime Annereau, Audrey Thomas-Schoemann, Carole Nicco-Overney, Christiane Chéreau, Frédéric Batteux, Jérôme Alexandre, François Lemare
A disintegrin and metalloproteinase 9 (ADAM9) possesses potent metastasis-inducing capacities and is highly expressed in several cancer cells. Previous work has shown that ADAM9 participates in the adhesive-invasive phenotype in lung cancer cells in vitro. In this study, we evaluated whether ADAM9 expression plays a critical role in metastatic processes in vivo and in angiogenesis. We first found that high ADAM9 expression was correlated with poor lung adenocarcinoma patient prognosis on Prognoscan data base...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28673571/high-altitude-and-pre-eclampsia-adaptation-or-protection
#20
Sarah I Y Ahmed, Muntaser E Ibrahim, Eltahir A G Khalil
Adaptive genes of high altitude can also be protective in diseases like preeclampsia, hypertension, and diabetes mellitus, Alzheimer, Parkinson Disease and Cancer, which may result from deregulation of hypoxia pathway. The example of pre-eclampsia and normal pregnancy were studied to see if the hypoxia-induced disorders can be dragged towards adaptation. Here, we analyse the genetic variants that are known to be associated with adaptation to high altitude hypoxia. Our results demonstrated that the genetic variants of EPAS1, ADAM9, and EGLN1 increased approximately three-fold in the cases of preeclampsia compared to normal pregnancy...
July 2017: Medical Hypotheses
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