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https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#1
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28915654/daurinol-blocks-breast-and-lung-cancer-metastasis-and-development-by-inhibition-of-focal-adhesion-kinase-fak
#2
Jong Kyu Woo, Hyun Jin Jung, Ji-Youn Park, Ju-Hee Kang, Byung Il Lee, DongYun Shin, Chu Won Nho, Soo-Young Cho, Je Kyung Seong, Seung Hyun Oh
FAK overexpression has been reported in diverse primary and metastatic tumor tissues, supporting its pro-tumorigenic and pro-metastatic roles. Therefore, we have developed a neo-treatment strategy using daurinol to effectively treat cancer metastasis. Daurinol blocked cancer cell migration and invasion in vitro and exhibited anti-metastatic activity in an experimental metastasis model of breast and lung cancer. Daurinol selectively inhibited phosphorylation of FAK at Tyr925, Tyr576/577, and Tyr397 sites in a dose- and time-dependent manner...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912559/inherent-aggressive-character-of-invasive-and-non-invasive-cells-dictates-the-in-vitro-migration-pattern-of-multicellular-spheroid
#3
Sukanya Gayan, Abhishek Teli, Tuli Dey
Cellular migration, a process relevant to metastasis, is mostly studied in the conventional 2D condition. However, cells cultured in the 3D condition assumed to mimic the in vivo conditions better. The current study is designed to compare an invasive and non-invasive adenocarcinoma cell with an invasive fibrosarcoma cell to understand the migration pattern of the multicellular spheroid. It is observed that conventional haplotaxis, chemotactic and pseudo-3D migration assay cannot distinguish between the invasive and non-invasive cells conclusively under 2D condition...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912543/inhibition-of-fucosylation-by-2-fluorofucose-suppresses-human-liver-cancer-hepg2-cell-proliferation-and-migration-as-well-as-tumor-formation
#4
Ying Zhou, Tomohiko Fukuda, Qinglei Hang, Sicong Hou, Tomoya Isaji, Akihiko Kameyama, Jianguo Gu
Core fucosylation is one of the most important glycosylation events in the progression of liver cancer. For this study, we used an easily handled L-fucose analog, 2-fluoro-L-fucose (2FF), which interferes with the normal synthesis of GDP-fucose, and verified its potential roles in regulating core fucosylation and cell behavior in the HepG2 liver cancer cell line. Results obtained from lectin blot and flow cytometry analysis clearly showed that 2FF treatment dramatically inhibited core fucosylation, which was also confirmed via mass spectrometry analysis...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911005/ociad2-suppressed-tumor-growth-and-invasion-via-akt-pathway-in-hepatocelluar-carcinoma
#5
Dan Wu, Xufang Yang, Huiming Peng, Dongmin Guo, Weiling Zhao, Chen Zhao, Xiaobo Zhou
Hepatocellular carcinoma (HCC) is an aggressive tumor and the third leading cause of cancer-related death worldwide. Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) has been found frequently methylated in various cancers, including HCC. The aim of the present study was to investigate the role of OCIAD2 in HCC progression. We analyzed liver hepatocellular carcinoma patients' data from the Cancer Genome Atlas (TCGA), including data extracted from 371 HCC tissues and 50 adjacent normal liver tissues...
September 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28910620/ctag-paperclip-reveals-alternative-polyadenylation-promotes-cell-type-specific-protein-diversity-and-shifts-araf-isoforms-with-microglia-activation
#6
Hun-Way Hwang, Yuhki Saito, Christopher Y Park, Nathalie E Blachère, Yoko Tajima, John J Fak, Ilana Zucker-Scharff, Robert B Darnell
Alternative polyadenylation (APA) is increasingly recognized to regulate gene expression across different cell types, but obtaining APA maps from individual cell types typically requires prior purification, a stressful procedure that can itself alter cellular states. Here, we describe a new platform, cTag-PAPERCLIP, that generates APA profiles from single cell populations in intact tissues; cTag-PAPERCLIP requires no tissue dissociation and preserves transcripts in native states. Applying cTag-PAPERCLIP to profile four major cell types in the mouse brain revealed common APA preferences between excitatory and inhibitory neurons distinct from astrocytes and microglia, regulated in part by neuron-specific RNA-binding proteins NOVA2 and PTBP2...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28904065/angptl1-interacts-with-integrin-%C3%AE-1%C3%AE-1-to-suppress-hcc-angiogenesis-and-metastasis-by-inhibiting-jak2-stat3-signaling
#7
Qian Yan, Lingxi Jiang, Ming Liu, Dandan Yu, Yu Zhang, Yan Li, Shuo Fang, Yan Li, Ying-Hui Zhu, Yunfei Yuan, Xin Yuan Guan
Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). Here we report that downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivo tumorigenicity, cell motility and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2 mediated anti-apoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903378/ago2-involves-the-malignant-phenotypes-and-fak-pi3k-akt-signaling-pathway-in-hypopharyngeal-derived-fadu-cells
#8
Yanhui Zhang, Baoxin Wang, Xinwei Chen, Weidong Li, Pin Dong
Argonaute 2 (AGO2) protein is usually overexpressed in various head and neck squamous cell carcinoma. However, the precise molecular mechanisms of AGO2 in hypopharyngeal cancer have not yet been clearly understood. Here we found the AGO2 expression in hypopharyngeal cancer tissues were generally higher comparing with that of the corresponding adjacent noncancerous epithelium tissues, and these were associated with the more aggressive clinicopathologic features and the poor clinical outcomes. Stable knockdown of AGO2 protein retarded cell proliferation, migration, invasion, arrested cell cycle and induced apoptosis...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899900/ret-receptor-tyrosine-kinase-sustains-proliferation-and-tissue-maturation-in-intestinal-epithelia
#9
Daniel Perea, Jordi Guiu, Bruno Hudry, Chrysoula Konstantinidou, Alexandra Milona, Dafni Hadjieconomou, Thomas Carroll, Nina Hoyer, Dipa Natarajan, Jukka Kallijärvi, James A Walker, Peter Soba, Nikhil Thapar, Alan J Burns, Kim B Jensen, Irene Miguel-Aliaga
Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation...
September 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28894469/ex-vivo-expansion-of-human-limbal-epithelial-cells-using-human-placenta-derived-and-umbilical-cord-derived-mesenchymal-stem-cells
#10
Sang Min Nam, Yong-Sun Maeng, Eung Kweon Kim, Kyoung Yul Seo, Helen Lew
Ex vivo culture of human limbal epithelial cells (LECs) is used to treat limbal stem cell (LSC) deficiency, a vision loss condition, and suitable culture systems using feeder cells or serum without animal elements have been developed. This study evaluated the use of human umbilical cord or placenta mesenchymal stem cells (C-MSCs or P-MSCs, resp.) as feeder cells in an animal/serum-free coculture system with human LECs. C-/P-MSCs stimulated LEC colony formation of the stem cell markers (p63, ABCG2) and secreted known LEC clonal growth factors (keratinocyte growth factor, β-nerve growth factor)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28894280/hypoxia-induced-angptl4-sustains-tumour-growth-and-anoikis-resistance-through-different-mechanisms-in-scirrhous-gastric-cancer-cell-lines
#11
Koichi Baba, Yoshihiko Kitajima, Shuusuke Miyake, Jun Nakamura, Kota Wakiyama, Hirofumi Sato, Keiichiro Okuyama, Hiroshi Kitagawa, Tomokazu Tanaka, Masatsugu Hiraki, Kazuyoshi Yanagihara, Hirokazu Noshiro
Patients with scirrhous gastric cancer (SGC) frequently develop peritoneal dissemination, which leads to poor prognosis. The secreted protein angiopoietin-like-4 (ANGPTL4), which is induced by hypoxia, exerts diverse effects on cancer progression. Here, we aimed to determine the biological function of ANGPTL4 in SGC cells under hypoxia. ANGPTL4 levels were higher in SGC cells under hypoxia than in other types of gastric cancer cells. Hypoxia-induced ANGPTL4 mRNA expression was regulated by hypoxia-inducible factor-1α (HIF-1α)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891248/integrin-fak-cdc42-pp1a-signaling-gnaws-at-yap-taz-activity-to-control-incisor-stem-cells
#12
REVIEW
Julia Hicks-Berthet, Xaralabos Varelas
How epithelial tissues are able to self-renew to maintain homeostasis and regenerate in response to injury remains a persistent question. The transcriptional effectors YAP and TAZ are increasingly being recognized as central mediators of epithelial stem cell biology, and a wealth of recent studies have been directed at understanding the control and activity of these factors. Recent work by Hu et al. has added to this knowledge, as they identify an Integrin-FAK-CDC42-PP1A signaling cascade that directs nuclear YAP/TAZ activity in stem cell populations of the mouse incisor, and define convergence on mTORC1 signaling as an important mediator of the proliferation of these cells...
September 11, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28882999/mir-193b-regulated-signaling-networks-serve-as-tumor-suppressors-in-liposarcoma-and-promote-adipogenesis-in-adipose-derived-stem-cells
#13
Ying Z Mazzu, Yulan Hu, Rajesh K Soni, Kelly M Mojica, Li-Xuan Qin, Phaedra Agius, Zachary M Waxman, Aleksandra Mihailovic, Nicholas D Socci, Ronald C Hendrickson, Thomas Tuschl, Samuel Singer
Well-differentiated and dedifferentiated liposarcomas (WDLS/DDLS) account for approximately 13% of all soft tissue sarcoma in adults and cause substantial morbidity or mortality in the majority of patients. In this study, we evaluated the functions of miRNA (miR-193b) in liposarcoma in vitro and in vivo. Deep RNA sequencing on 93 WDLS, 145 DDLS and 12 normal fat samples demonstrated that miR-193b was significantly underexpressed in DDLS compared to normal fat. Re-introduction of miR-193b induced apoptosis in liposarcoma cells and promoted adipogenesis in human adipose-derived stem cells (ASC)...
September 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28881794/enhanced-efficacy-of-akt-and-fak-kinase-combined-inhibition-in-squamous-cell-lung-carcinomas-with-stable-reduction-in-pten
#14
Andrea Cavazzoni, Silvia La Monica, Roberta Alfieri, Andrea Ravelli, Nele Van Der Steen, Rocco Sciarrillo, Denise Madeddu, Costanza Anna Maria Lagrasta, Federico Quaini, Mara Bonelli, Claudia Fumarola, Daniele Cretella, Graziana Digiacomo, Marcello Tiseo, Godefridus J Peters, Andrea Ardizzoni, Pier Giorgio Petronini, Elisa Giovannetti
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881682/inhibition-of-fak-kinase-activity-preferentially-targets-cancer-stem-cells
#15
Vihren N Kolev, Winnie F Tam, Quentin G Wright, Sean P McDermott, Christian M Vidal, Irina M Shapiro, Qunli Xu, Max S Wicha, Jonathan A Pachter, David T Weaver
Because cancer stem cells (CSCs) have been implicated in chemo-resistance, metastasis and tumor recurrence, therapeutic targeting of CSCs holds promise to address these clinical challenges to cancer treatment. VS-4718 and VS-6063 are potent inhibitors of focal adhesion kinase (FAK), a non-receptor tyrosine kinase that mediates cell signals transmitted by integrins and growth factor receptors. We report here that inhibition of FAK kinase activity by VS-4718 or VS-6063 preferentially targets CSCs, as demonstrated by a panel of orthogonal CSC assays in cell line models and surgically resected primary breast tumor specimens cultured ex vivo...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880199/the-role-of-focal-adhesion-kinase-in-keratinocyte-fibrogenic-gene-expression
#16
Michael Januszyk, Sun Hyung Kwon, Victor W Wong, Jagannath Padmanabhan, Zeshaan N Maan, Alexander J Whittam, Melanie R Major, Geoffrey C Gurtner
Abnormal skin scarring causes functional impairment, psychological stress, and high socioeconomic cost. Evidence shows that altered mechanotransduction pathways have been linked to both inflammation and fibrosis, and that focal adhesion kinase (FAK) is a key mediator of these processes. We investigated the importance of keratinocyte FAK at the single cell level in key fibrogenic pathways critical for scar formation. Keratinocytes were isolated from wildtype and keratinocyte-specific FAK-deleted mice, cultured, and sorted into single cells...
September 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28871113/trib3-inhibits-proliferation-and-promotes-osteogenesis-in-hbmscs-by-regulating-the-erk1-2-signaling-pathway
#17
Cui Zhang, Fan-Fan Hong, Cui-Cui Wang, Liang Li, Jian-Ling Chen, Fei Liu, Ren-Fu Quan, Jin-Fu Wang
Osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs) is regulated by various factors, including bone morphogenetic proteins (BMPs), Notch, growth hormones and mitogen-activated protein kinases (MAPKs). Tribbles homolog 3 (TRIB3), a pseudokinase, plays an important role in cancer cells and adipocytes. However, TRIB3 function in osteogenic differentiation is unknown, although it is involved in regulating signaling pathways associated with osteogenic differentiation. Here, we found that TRIB3 was highly expressed during osteogenic differentiation in hBMSCs...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869459/modulation-of-the-mesenchymal-stem-cell-migration-capacity-via-preconditioning-with-topographic-microstructure
#18
Zhengdong Li, Xun Xu, Weiwei Wang, Karl Kratz, Xianlei Sun, Jie Zou, Zijun Deng, Friedrich Jung, Manfred Gossen, Nan Ma, Andreas Lendlein
Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted and persisted by brief preconditioning with the appropriate microtopography...
August 28, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28867754/sushi-repeat-containing-protein-x-linked-2-promotes-angiogenesis-through-the-urokinase-type-plasminogen-activator-receptor-dependent-integrin-%C3%AE-v%C3%AE-3-focal-adhesion-kinase-pathways
#19
Kuiliang Liu, Jianghao Fan, Jing Wu
Sushi repeat-containing protein X-linked 2 (SRPX2) is a newly identified chondroitin sulfate proteoglycan that is markedly elevated in multiple solid tumors. It is also suggested that SRPX2 is associated with angiogenesis. A conditioned medium of SRPX2 overexpressing colorectal cancer (CRC) cells and SRPX2 recombinant protein was used to evaluate the effect of secretory SRPX2 on the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) and the involved molecular mechanisms. It was revealed that the activity of SRPX2 is dependent on the urokinase-type plasminogen activator receptor and cooperation of the integrin αvβ3 co-receptor...
2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28863189/opposing-effects-of-in-vitro-differentiated-macrophages-sub-type-on-epithelial-wound-healing
#20
Julia A Gindele, Samuel Mang, Nicolas Pairet, Ingrid Christ, Florian Gantner, Jürgen Schymeinsky, David J Lamb
Inappropriate repair responses to pulmonary epithelial injury have been linked to perturbation of epithelial barrier function and airway remodelling in a number of respiratory diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. We developed an in vitro mechanical scratch injury model in air-liquid interface differentiated primary human small airway epithelial cells that recapitulates many of the characteristics observed during epithelial wound injury in both human tissue and small animal models...
2017: PloS One
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