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https://www.readbyqxmd.com/read/28442586/therapeutic-targeting-of-ptk7-is-cytotoxic-in-atypical-teratoid-rhabdoid-tumors
#1
Shanta M Messerli, Mariah M Hoffman, Etienne Z Gnimpieba, Ratan D Bhardwaj
Novel discoveries involving the evaluation of potential therapeutics are based on newly identified molecular targets for atypical teratoid rhabdoid tumors (ATRT), which are the most common form of infantile brain tumors. Central nervous system ATRTs are rare, aggressive, and fast growing tumors of the brain and spinal cord and carry a very poor prognosis. Currently, the standard of care for ATRT patients is based on surgical resection followed by systemic chemotherapy and radiation therapy, which result in severe side effects...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28424771/ptk7-faces-the-wnt-in-development-and-disease
#2
REVIEW
Hanna Berger, Andreas Wodarz, Annette Borchers
PTK7 (protein tyrosine kinase 7) is an evolutionarily conserved transmembrane receptor regulating various processes in embryonic development and tissue homeostasis. On a cellular level PTK7 affects the establishment of cell polarity, the regulation of cell movement and migration as well as cell invasion. The PTK7 receptor has been shown to interact with ligands, co-receptors, and intracellular transducers of Wnt signaling pathways, pointing to a function in the fine-tuning of the Wnt signaling network. Here we will review recent findings implicating PTK7 at the crossroads of Wnt signaling pathways in development and disease...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28420671/ptk7-localization-and-protein-stability-is-affected-by-canonical-wnt-ligands
#3
Hanna Berger, Marlen Breuer, Hanna Peradziryi, Martina Podleschny, Ralf Jacob, Annette Borchers
PTK7 (protein tyrosine kinase 7) is an evolutionarily conserved transmembrane receptor with important roles in embryonic development and disease. Originally identified as a gene upregulated in colon cancer it was later shown to regulate planar cell polarity (PCP) and directional cell movement. PTK7 is a Wnt co-receptor, however its role in Wnt signaling remains controversial. Here, we find evidence that place PTK7 at the intersection of canonical and non-canonical Wnt signaling pathways. In presence of canonical Wnt ligands PTK7 is subject to caveolin-mediated endocytosis, while it is unaffected by non-canonical Wnt ligands...
April 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28249716/conserved-effect-of-aging-on-dna-methylation-and-association-with-ezh2-polycomb-protein-in-mice-and-humans
#4
Khyobeni Mozhui, Ashutosh K Pandey
In humans, DNA methylation at specific CpG sites can be used to estimate the 'epigenetic clock', a biomarker of aging and health. The mechanisms that regulate the aging epigenome and level of conservation are not entirely clear. We performed affinity-based enrichment with methyl-CpG binding domain protein followed by high-throughput sequencing (MBD-seq) to assay DNA methylation in mouse samples. Consistent with previous reports, aging is associated with increase in methylation at CpG islands that likely overlap regulatory regions of genes that have been implicated in cancers (e...
March 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28229174/characterization-of-the-specific-interaction-between-the-dna-aptamer-sgc8c-and-protein-tyrosine-kinase-7-receptors-at-the-surface-of-t-cells-by-biosensing-afm
#5
Michael Leitner, Alexandra Poturnayova, Constanze Lamprecht, Sabine Weich, Maja Snejdarkova, Ivana Karpisova, Tibor Hianik, Andreas Ebner
We studied the interaction of the specific DNA aptamer sgc8c immobilized at the AFM tip with its corresponding receptor, the protein tyrosine kinase-7 (PTK7) embedded in the membrane of acute lymphoblastic leukemia (ALL) cells (Jurkat T-cells). Performing single molecule force spectroscopy (SMFS) experiments, we showed that the aptamer sgc8c bound with high probability (38.3 ± 7.48%) and high specificity to PTK7, as demonstrated by receptor blocking experiments and through comparison with the binding behavior of a nonspecific aptamer...
April 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28089349/development-of-new-ptk7-targeting-aptamer-fluorescent-and-radiolabelled-probes-for-evaluation-as-molecular-imaging-agents-lymphoma-and-melanoma-in-vivo-proof-of-concept
#6
Victoria Calzada, María Moreno, Jessica Newton, Joel González, Marcelo Fernández, Juan Pablo Gambini, Manuel Ibarra, Alejandro Chabalgoity, Susan Deutscher, Thomas Quinn, Pablo Cabral, Hugo Cerecetto
Aptamers are single-stranded oligonucleotides that recognize molecular targets with high affinity and specificity. Aptamer that selectively bind to the protein tyrosine kinase-7 (PTK7) receptor, overexpressed on many cancers, has been labelled as probes for molecular imaging of cancer. Two new PTK7-targeting aptamer probes were developed by coupling frameworks from the fluorescent dye AlexaFluor647 or the 6-hydrazinonicotinamide (HYNIC) chelator-labelled to (99m)Tc. The derivatizations via a 5'-aminohexyl terminal linker were done at room temperature and under mild buffer conditions...
December 24, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28077676/a-ptk7-targeted-antibody-drug-conjugate-reduces-tumor-initiating-cells-and-induces-sustained-tumor-regressions
#7
Marc Damelin, Alexander Bankovich, Jeffrey Bernstein, Justin Lucas, Liang Chen, Samuel Williams, Albert Park, Jorge Aguilar, Elana Ernstoff, Manoj Charati, Russell Dushin, Monette Aujay, Christina Lee, Hanna Ramoth, Milly Milton, Johannes Hampl, Sasha Lazetic, Virginia Pulito, Edward Rosfjord, Yongliang Sun, Lindsay King, Frank Barletta, Alison Betts, Magali Guffroy, Hadi Falahatpisheh, Christopher J O'Donnell, Robert Stull, Marybeth Pysz, Paul Escarpe, David Liu, Orit Foord, Hans Peter Gerber, Puja Sapra, Scott J Dylla
Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/27689325/catalytically-defective-receptor-protein-tyrosine-kinase-ptk7-enhances-invasive-phenotype-by-inducing-mmp-9-through-activation-of-ap-1-and-nf-%C3%AE%C2%BAb-in-esophageal-squamous-cell-carcinoma-cells
#8
Won-Sik Shin, Yuri Hong, Hae Won Lee, Seung-Taek Lee
Protein tyrosine kinase 7 (PTK7), a member of the catalytically defective receptor protein tyrosine kinase family, is upregulated in various cancers including esophageal squamous cell carcinoma (ESCC). Here, we have explored the molecular mechanism of PTK7-dependent invasiveness in ESCC cells. PTK7 knockdown reduced gelatin degradation and MMP-9 secretion in cultures of ESCC TE-10 cells, and showed reduced levels of MMP9 mRNA using real-time RT-PCR and luciferase reporter assays. PTK7 knockdown decreased not only phosphorylation of NF-κB, IκB, ERK, and JNK, but also nuclear localization of NF-κB and AP-1 consisting of c-Fos and c-Jun...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27557627/ptk7-regulates-radioresistance-through-nuclear-factor-kappa-b-in-esophageal-squamous-cell-carcinoma
#9
Misun Park, Hyeon-Joon Yoon, Moon Chul Kang, Junhye Kwon, Hae Won Lee
Tumor radioresistance is a major reason for decreased efficiency of cancer radiation therapy. Although a number of factors involved in radioresistance have been identified, the molecular mechanisms underlying radioresistance of esophageal squamous cell carcinoma (ESCC) have not been elucidated. In this study, we investigated the role of oncogenic protein tyrosine kinase 7 (PTK7) in the resistance of ESCC to radiation therapy. ESCC cell lines with high PTK7 expression were more refractive to radiation than those with low PTK7 levels...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27499181/ptk7-overexpression-in-colorectal-tumors-clinicopathological-correlation-and-prognosis-relevance
#10
Xiuyun Tian, Liang Yan, Donghai Zhang, Xiaoya Guan, Bin Dong, Min Zhao, Chunyi Hao
Colorectal cancer (CRC) has one of the highest mortality rates in the worldwide and its incidence has been increasing in recent years. Protein tyrosine kinase-7 (PTK7) is an inactive member of receptor protein tyrosine kinase (RPTK)-like molecules, which is involved in tumorigenesis of a variety of cancers. Our study aimed to investigate expression of PTK7 in colorectal tumors (including benign adenomas and malignant carcinomas), and its potential function in tumorigenesis and prognosis. A total of 209 CRC patients and 28 colonic adenoma patients were included in this study...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27438854/ptk7-and-mcc-unfancied-components-in-non-canonical-wnt-signaling-and-cancer
#11
REVIEW
Norris Ray Dunn, Nicholas S Tolwinski
Human development uses a remarkably small number of signal transduction pathways to organize vastly complicated tissues. These pathways are commonly associated with disease in adults if activated inappropriately. One such signaling pathway, Wnt, solves the too few pathways conundrum by having many alternate pathways within the Wnt network. The main or "canonical" Wnt pathway has been studied in great detail, and among its numerous downstream components, several have been identified as drug targets that have led to cancer treatments currently in clinical trials...
2016: Cancers
https://www.readbyqxmd.com/read/27284198/zebrafish-models-of-idiopathic-scoliosis-link-cerebrospinal-fluid-flow-defects-to-spine-curvature
#12
D T Grimes, C W Boswell, N F C Morante, R M Henkelman, R D Burdine, B Ciruna
Idiopathic scoliosis (IS) affects 3% of children worldwide, yet the mechanisms underlying this spinal deformity remain unknown. Here we show that ptk7 mutant zebrafish, a faithful developmental model of IS, exhibit defects in ependymal cell cilia development and cerebrospinal fluid (CSF) flow. Transgenic reintroduction of Ptk7 in motile ciliated lineages prevents scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes yields IS phenotypes. We define a finite developmental window for motile cilia in zebrafish spine morphogenesis...
June 10, 2016: Science
https://www.readbyqxmd.com/read/27183644/ptk7-deficient-mice-have-decreased-hematopoietic-stem-cell-pools-as-a-result-of-deregulated-proliferation-and-migration
#13
Anne-Catherine Lhoumeau, Marie-Laure Arcangeli, Maria De Grandis, Marilyn Giordano, Jean-Christophe Orsoni, Frédérique Lembo, Florence Bardin, Sylvie Marchetto, Michel Aurrand-Lions, Jean-Paul Borg
Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. At the top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features are controlled through key microenvironmental cues and regulatory pathways, such as Wnt signaling. We showed previously that PTK7, a tyrosine kinase receptor involved in planar cell polarity, plays a role in epithelial Wnt signaling; however, its function in hematopoiesis has remained unexplored...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27101533/ultrasensitive-electrochemical-detection-of-protein-tyrosine-kinase-7-by-gold-nanoparticles-and-methylene-blue-assisted-signal-amplification
#14
Xiangmin Miao, Zongbing Li, Aihua Zhu, Zhaozhong Feng, Jun Tian, Xue Peng
We present here an ultrasensitive and simple strategy for protein tyrosine kinase-7 (PTK7) detection based on the recognition-induced structure change of sgc8 aptamer, and the signal change of methylene blue (MB) that interacted with sandwiched DNA complex. To construct such a sensor, an homogeneous nano-surface was formed firstly on the glass carbon electrode (GCE) by using negatively charged Nafion (Nf) as the inner layer and positively charged gold nanoparticles ((+)AuNPs) as the outer layer, followed by the immobilization of sgc8 aptamer based on Au-S bond...
September 15, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27074666/wnt-ptk7-and-fgfrl-expression-gradients-control-trunk-positional-identity-in-planarian-regeneration
#15
Rachel Lander, Christian P Petersen
Mechanisms enabling positional identity re-establishment are likely critical for tissue regeneration. Planarians use Wnt/beta-catenin signaling to polarize the termini of their anteroposterior axis, but little is known about how regeneration signaling restores regionalization along body or organ axes. We identify three genes expressed constitutively in overlapping body-wide transcriptional gradients that control trunk-tail positional identity in regeneration. ptk7 encodes a trunk-expressed kinase-dead Wnt co-receptor, wntP-2 encodes a posterior-expressed Wnt ligand, and ndl-3 encodes an anterior-expressed homolog of conserved FGFRL/nou-darake decoy receptors...
2016: ELife
https://www.readbyqxmd.com/read/26944093/protein-tyrosine-kinase-7-is-essential-for-tubular-morphogenesis-of-the-wolffian-duct
#16
Bingfang Xu, Angela M Washington, Raquel Fantin Domeniconi, Ana Cláudia Ferreira Souza, Xiaowei Lu, Ann Sutherland, Barry T Hinton
The Wolffian duct, the proximal end of the mesonephric duct, undergoes non-branching morphogenesis to achieve an optimal length and size for sperm maturation. It is important to examine the mechanisms by which the developing mouse Wolffian duct elongates and coils for without proper morphogenesis, male infertility will result. Here we show that highly proliferative epithelial cells divide in a random orientation relative to the elongation axis in the developing Wolffian duct. Convergent extension (CE)-like of cell rearrangements is required for elongating the duct while maintaining a relatively unchanged duct diameter...
April 15, 2016: Developmental Biology
https://www.readbyqxmd.com/read/26829210/multiparametric-flow-cytometric-analysis-of-whole-blood-reveals-changes-in-minor-lymphocyte-subpopulations-of-multiple-sclerosis-patients
#17
Aina Teniente-Serra, Laia Grau-López, M José Mansilla, Marco Fernández-Sanmartín, Anna Ester Condins, Cristina Ramo-Tello, Eva Martínez-Cáceres
OBJECTIVE: The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up. MATERIAL AND METHODS: Peripheral blood from 40 healthy donors (HD) and 66 MS patients [23 relapsing-remitting (RRMS) without treatment, 27 RRMS undergoing treatment (16 IFN-β, 11 natalizumab), and 16 progressive forms (eight secondary progressive and eight primary progressive)] was analysed by multiparametric flow cytometry...
June 2016: Autoimmunity
https://www.readbyqxmd.com/read/26680417/a-ptk7-ror2-co-receptor-complex-affects-xenopus-neural-crest-migration
#18
Martina Podleschny, Anita Grund, Hanna Berger, Erik Rollwitz, Annette Borchers
Neural crest cells are a highly migratory pluripotent cell population that generates a wide array of different cell types and failure in their migration can result in severe birth defects and malformation syndromes. Neural crest migration is controlled by various means including chemotaxis, repellent guidance cues and cell-cell interaction. Non-canonical Wnt PCP (planar cell polarity) signaling has previously been shown to control cell-contact mediated neural crest cell guidance. PTK7 (protein tyrosine kinase 7) is a transmembrane pseudokinase and a known regulator of Wnt/PCP signaling, which is expressed in Xenopus neural crest cells and required for their migration...
2015: PloS One
https://www.readbyqxmd.com/read/26642056/in-utero-cigarette-smoke-affects-allergic-airway-disease-but-does-not-alter-the-lung-methylome
#19
Kenneth R Eyring, Brent S Pedersen, Ivana V Yang, David A Schwartz
Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA)...
2015: PloS One
https://www.readbyqxmd.com/read/26631510/quantitative-profiling-of-protein-tyrosine-kinases-in-human-cancer-cell-lines-by-multiplexed-parallel-reaction-monitoring-assays
#20
Hye-Jung Kim, De Lin, Hyoung-Joo Lee, Ming Li, Daniel C Liebler
Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run...
February 2016: Molecular & Cellular Proteomics: MCP
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