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https://www.readbyqxmd.com/read/29791208/human-soluble-phospholipase-a-2-receptor-is-an-inhibitor-of-the-integrin-mediated-cell-migratory-response-to-collagen-i
#1
Kazunori Watanabe, Kazuhiro Watanabe, Yosuke Watanabe, Daisuke Fujioka, Takamitsu Nakamura, Kazuto Nakamura, Jun-Ei Obata, Kiyotaka Kugiyama
Murine membrane-bound phospholipase A2 receptor 1 (PLA2 R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA2 R. This study examined whether human soluble PLA2 R may have biological functions and whether soluble PLA2 R may exist in human plasma. Here, we showed that human recombinant soluble PLA2 R (rsPLA2 R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin β1 on the cell surface of HEK293 cells...
May 23, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29787750/erybraedin-a-is-a-potential-src-inhibitor-that-blocks-the-adhesion-and-viability-of-non-small-cell-lung-cancer-cells
#2
Hye-Young Min, Yujin Jung, Kwan Hee Park, Won Keun Oh, Ho-Young Lee
The adhesion of cancer cells to the extracellular matrix (ECM) is crucial for cell proliferation, survival, and metastasis. Thus, it is necessary to inhibit cell-ECM adhesion by blocking the activation of the associated signaling to control cancer. Here, we identify erybraedin A (EBA) as a potential Src inhibitor that blocks cell adhesion and viability in non-small-cell lung cancer (NSCLC). EBA significantly inhibited the adhesion of NSCLC cells to fibronectin. EBA also markedly inhibited the activation of Src and its downstream targets, including FAK and Akt...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29786754/regulation-of-interferon-signaling-and-hcv%C3%A2-rna-replication-by-extracellular-matrix
#3
Takuya Kuwashiro, Shinji Iwane, Xia Jinghe, Sachiko Matsuhashi, Yuichiro Eguchi, Keizo Anzai, Kazuma Fujimoto, Toshihiko Mizuta, Naoya Sakamoto, Masanori Ikeda, Nobuyuki Kato, Iwata Ozaki
Although interferon (IFN)‑based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH‑7 human hepatoma cell line and HuH‑7 cells were stably transfected with full‑length HCV‑RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM‑coated dishes or non‑coated plastic dishes (NDs), and treated with human IFN‑α...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786069/ve-cadherin-promotes-vasculogenic-mimicry-by-modulating-kaiso-dependent-gene-expression
#4
Daniel Delgado-Bellido, Mónica Fernández-Cortés, María Isabel Rodríguez, Santiago Serrano-Sáenz, Arkaitz Carracedo, Angel Garcia-Diaz, F Javier Oliver
Aberrant extra-vascular expression of VE-cadherin (VEC) has been observed in metastasis associated with vasculogenic mimicry (VM); however, the ultimate reason why non-endothelial VEC favors the acquisition of this phenotype is not established. In this study, we show that human malignant melanoma cells have a constitutively high expression of phoshoVEC (pVEC) at Y658; pVEC is a target of focal adhesion kinase (FAK) and forms a complex with p120-catenin and the transcriptional repressor kaiso in the nucleus...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785119/clinical-relevance-of-lysyl-oxidase-like-2-and-functional-mechanisms-in-glioma
#5
Xiao-Guang Du, Mei-Jia Zhu
Introduction: Glioma is the most frequent malignancy of the adult central nervous system with high recurrence risk and poor prognosis. Understanding the biological molecular mechanisms involved in glioma progression is critical for studying oncogenic mechanisms and improving prognosis. Lysyl oxidase-like 2 (LOXL2) is a kind of lysyl oxidase catalyzing the formation of peptidyl-lysine residues and promoting intramolecular cross-linking, especially for proteins in extracellular matrix. Our study explored the expression pattern of LOXL2 in glioma for the first time and found that its high expression was associated with larger tumor size and advanced tumor grade ( P <0...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29784011/extremely-low-frequency-electromagnetic-fields-promote-mesenchymal-stem-cell-migration-by-increasing-intracellular-ca-2-and-activating-the-fak-rho-gtpases-signaling-pathways-in-vitro
#6
Yingchi Zhang, Jiyuan Yan, Haoran Xu, Yong Yang, Wenkai Li, Hua Wu, Chaoxu Liu
BACKGROUND: The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. METHODS: We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29782351/role-of-lkb1-in-migration-and-invasion-of-cr-vi-transformed-human-bronchial-epithelial-beas-2b-cells
#7
Jian Lu, Zhongping Zhou, Miaomiao Tang, Haijun Shen, Yi Liu, Jin Wang, Yewen Jiang, Yifan Chen, Zhanao Wu
Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epithelial cells. The mechanism underlying its carcinogenicity is unclear in terms of how it facilitates metastases. Cr(VI) compounds are reported to briefly promote cell migration in a concentration-dependent manner and oncogene liver kinase B1 (LKB1) was reduced in Cr(VI)-transformed cells. Overexpression of LKB1 in Beas-2B-Cr [Cr(VI) malignantly transformed Beas-2B cells] suppressed cell migration and invasion and inactivated FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, which contribute to cell migration and invasion...
May 18, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29782321/pyk2-is-a-novel-tau-tyrosine-kinase-that-is-regulated-by-the-tyrosine-kinase-fyn
#8
Chuanzhou Li, Jürgen Götz
The protein tyrosine kinase Pyk2 is encoded by PTK2B, a novel Alzheimer's disease (AD) susceptibility variant, with the PTK2B risk allele being associated with increased mRNA levels, suggestive of increased Pyk2 levels. However, the role of Pyk2, a member of the focal adhesion kinase (FAK) family, in AD pathology and its regulation are largely unknown. To address this, we generated mice with neuronal expression of human Pyk2. Because we had previously reported an association of Pyk2 and hyperphosphorylated tau (a hallmark feature of AD) in human tau transgenic pR5 mice, we also generated Pyk2/tau double-transgenic mice, which exhibit increased tyrosine phosphorylation and accumulation of tau...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29780168/lox-catalyzed-collagen-stabilization-is-a-proximal-cause-for-intrinsic-resistance-to-chemotherapy
#9
Leonie Rossow, Simona Veitl, Sandra Vorlová, Jacqueline K Wax, Anja E Kuhn, Verena Maltzahn, Berin Upcin, Franziska Karl, Helene Hoffmann, Sabine Gätzner, Matthias Kallius, Rajender Nandigama, Daniela Scheld, Ster Irmak, Sabine Herterich, Alma Zernecke, Süleyman Ergün, Erik Henke
The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29778566/lung-squamous-cell-carcinoma-cells-express-non-canonically-glycosylated-igg-that-activates-integrin-fak-signaling
#10
Jingshu Tang, Jingxuan Zhang, Yang Liu, Qinyuan Liao, Jing Huang, Zihan Geng, Weiyan Xu, Zhengzuo Sheng, Gregory Lee, Youhui Zhang, Jinfeng Chen, Liang Zhang, Xiaoyan Qiu
It is increasingly recognized that many human carcinomas express immunoglobulin (Ig) molecules that are distinct from B-cell-derived Ig and play important roles in cancer initiation, progression, and metastasis. However, the molecular mechanisms underlying the functions of cancer-derived Ig remain elusive. Here, we report that lung squamous cell carcinoma (LSCC) cells frequently express high levels of cancer IgG (CIgG) that is specifically recognized by a monoclonal antibody RP215. RP215 recognizes CIgG via a novel epitope that involves an N-glycan modification at a non-consensus site within the CH 1 domain...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777904/axed-muc4-muc4-x-aggravates-pancreatic-malignant-phenotype-by-activating-integrin-%C3%AE-1-fak-erk-pathway
#11
Rahat Jahan, Muzafar A Macha, Satyanarayana Rachaghani, Srustidhar Das, Lynette M Smith, Sukhwinder Kaur, Surinder K Batra
Alternative splicing is evolving as an eminent player of oncogenic signaling for tumor development and progression. Mucin 4 (MUC4), a type I membrane-bound mucin, is differentially expressed in pancreatic cancer (PC) and plays a critical role in its progression and metastasis. However, the molecular implications of MUC4 splice variants during disease pathogenesis remain obscure. The present study delineates the pathological and molecular significance of a unique splice variant of MUC4, MUC4/X, which lacks the largest and polymorphic exon 2, along with exon 3...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777737/type-i-collagen-induces-mesenchymal-cell-differentiation-into-myofibroblasts-through-yap-induced-tgf-%C3%AE-1-activation
#12
Xiaoling Liu, Xinyu Long, Weiwei Liu, Yeli Zhao, Toshihiko Hayashi, Masayuki Yamato, Kazunori Mizuno, Hitomi Fujisaki, Shunji Hattori, Shin-Ichi Tashiro, Takaaki Ogura, Yuji Atsuzawa, Takashi Ikejima
In organ fibrosis, mechanical stress and transforming growth factor beta-1 (TGF-β1) promote differentiation into myofibroblast from mesenchymal cells, leading to extracellular matrix (ECM) remodeling or active synthesis, deposition or degradation of ECM components. A major component of ECM, type I collagen (col I) triple helical molecules assemble into fibrils or are denatured to gelatin without triple-helicity in remodeling. However, whether changes of ECM components in remodeling have influence on mesenchymal cell differentiation remains elusive...
May 16, 2018: Biochimie
https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#13
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777374/the-tenascin-c-derived-peptide-vswrapta-promotes-neuronal-branching-via-transcellular-activation-of-the-focal-adhesion-kinase-fak-and-the-erk1-2-signaling-pathway-in-vitro
#14
Marvin Jarocki, Omar Sallouh, Ralf Weberskirch, Andreas Faissner
The central nervous system (CNS) of mammals has a limited regeneration capacity after traumatic events, which causes chronic functional disability. The development of biomaterials aims at providing support for the regeneration process. One strategy integrates peptides that mimic functional domains of extracellular matrix (ECM) or cell adhesion molecules with synthetic polymers designed to present growth-supporting cues to the neuronal microenvironment. Thus, small peptide sequences originating from molecules of the ECM may serve as promising bio-additives, acting as artificial matricryptins to gear cellular processes...
May 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29775632/controlled-delivery-of-a-focal-adhesion-kinase-inhibitor-results-in-accelerated-wound-closure-with-decreased-scar-formation
#15
Kun Ma, Sun Hyung Kwon, Jagannath Padmanabhan, Dominik Duscher, Artem A Trotsyuk, Yixiao Dong, Mohammed Inayathullah, Jayakumar Rajadas, Geoffrey C Gurtner
Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries...
May 15, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29774119/periostin-a-signal-transduction-intermediate-in-tgf-%C3%AE-induced-emt-in-u-87mg-human-glioblastoma-cells-and-its-inhibition-by-anthocyanidins
#16
Amira Ouanouki, Sylvie Lamy, Borhane Annabi
Periostin is a secreted protein that is highly expressed in glioblastoma cells as compared to normal brain tissue, and is therefore considered as a potential biomarker in therapeutic modalities. Its contribution in the cancer cells invasive phenotype is, however, poorly understood. This work investigates the role of periostin in U-87 MG glioblastoma cell invasion, cell migration and in Transforming Growth Factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT). Periostin gene silencing, using small interfering RNA, decreased TGF-β-induced mesenchymal marker expression of fibronectin and vimentin, partly through reduced Smad2, Akt and Fak phosphorylation as well as U-87 MG cell invasion and migration...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773903/circadian-regulator-nr1d2-regulates-glioblastoma-cell-proliferation-and-motility
#17
Min Yu, Wenjing Li, Qianqian Wang, Yan Wang, Fei Lu
Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29766567/melatonin-attenuates-osteosarcoma-cell-invasion-by-suppression-of-c-c-motif-chemokine-ligand-24-through-inhibition-of-the-c-jun-n-terminal-kinase-pathway
#18
Ko-Hsiu Lu, Shih-Chi Su, Chiao-Wen Lin, Yi-Hsien Hsieh, Ya-Chiu Lin, Ming-Hsien Chien, Russel J Reiter, Shun-Fa Yang
Osteosarcoma, with its high metastatic potential, is the most prevalent malignant bone tumor in children and adolescents. Melatonin possesses multiple tumor-suppressing properties for a myriad of tumors, but little is known about the effects of melatonin on osteosarcoma metastasis. In this study, we demonstrated that melatonin elicited very low cytotoxicity and significantly inhibited cellular motility, migration, and invasion in human osteosarcoma U2OS and HOS cells. Moreover, using RNA sequencing technology, we revealed that melatonin repressed C-C motif chemokine ligand 24 (CCL24) gene expression in U2OS cells...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29765540/could-a-plant-derived-protein-potentiate-the-anticancer-effects-of-a-stem-cell-in-brain-cancer
#19
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Cost, Heron Fernandes Vieira Torquato, Natalia Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma is the most aggressive brain tumor with poor overall survival bellow 2 years. The natural compounds with anti-cancer properties, are thus gaining attention for possible adjuvant GBM treatment. In various cancer models Enterolobium contortisiliquum Trypsin Inhibitor (EcTI) proved to have anti-cancer effects. Here, we investigated the EcTI effects on GBM U87 cells and on mesenchymal stem cells (MSC) compared to their direct coculture (MSC/U87). MSC are present in tumor stroma, modulating GBM cells phenotype, and also represent potential drug delivery vehicle due to their tumor tropism...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29763414/cd93-promotes-integrin-%C3%AE-1-activation-and-fibronectin-fibrillogenesis-during-tumor-angiogenesis
#20
Roberta Lugano, Kalyani Vemuri, Di Yu, Michael Bergqvist, Anja Smits, Magnus Essand, Staffan Johansson, Elisabetta Dejana, Anna Dimberg
Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is up-regulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates integrin-β1-signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation...
May 15, 2018: Journal of Clinical Investigation
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