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Fyn melanoma

Zhi-Kun Yang, Jing-Yun Yang, Zhuo-Zai Xu, Wei-Hong Yu
Objective: The objective of the study was to summarize the role of DNA methylation in the development and metastasis of uveal melanoma (UM). Data Sources: The relevant studies in MEDLINE were searched. Study Selection: In this review, we performed a comprehensive literature search in MEDLINE using "uveal melanoma" AND ("DNA methylation" OR "epigenetics") for original research/review articles published before February 2018 on the relationship between DNA methylation and UM...
April 5, 2018: Chinese Medical Journal
Marie Christine Martens, Christina Seebode, Janin Lehmann, Steffen Emmert
UV radiation is acknowledged as the primary cause of photocarcinogenesis and therefore contributes to the development of skin cancer entities such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. Typical DNA photoproducts and indirect DNA damage caused by reactive oxygen species are the result of UV radiation. UV-induced DNA damage is repaired by nucleotide excision repair, which consequently counteracts the development of mutations and skin carcinogenesis. Tumour-suppressor genes are inactivated by mutation and growth-promoting pathways are activated leading to disruption of cell-cycle progression...
February 2018: Anticancer Research
Hazuki Yamada, Koji Tsutsumi, Yuki Nakazawa, Yoshio Shibagaki, Seisuke Hattori, Yasutaka Ohta
FilGAP is a Rac-specific GTPase-activating protein (GAP) that suppresses lamellae formation. In this study, we have identified RBM10 (RNA Binding Motif domain protein 10) as a FilGAP-interacting protein. Although RBM10 is mostly localized in the nuclei in human melanoma A7 cells, forced expression of Src family tyrosine kinase Fyn induced translocation of RBM10 from nucleus into cell peripheries where RBM10 and FilGAP are co-localized. The translocation of RBM10 from nucleus appears to require catalytic activity of Fyn since kinase-negative Fyn mutant failed to induce translocation of RBM10 in A7 cells...
2016: PloS One
Daniel Elias, Henrik J Ditzel
Fyn is a non-receptor tyrosine kinase that belongs to the Src family kinases (SFKs) which under normal physiological conditions is involved in signal transduction pathways in the nervous system, as well as the development and activation of T lymphocytes. In cancer, Fyn contributes to the development and progression of several cancer types through its involvement in the control of cell growth, death, morphogenic transformation and cellular motility. Enhanced expression and/or activation of Fyn is observed in various cancers, including melanoma, glioblastoma, squamous cell carcinoma, prostate and breast cancers...
October 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jaume Folch, Dmitry Petrov, Miren Ettcheto, Ignacio Pedrós, Sonia Abad, Carlos Beas-Zarate, Alberto Lazarowski, Miguel Marin, Jordi Olloquequi, Carme Auladell, Antoni Camins
Alzheimer's disease (AD) is a degenerative neurological disorder that is the most common cause of dementia and disability in older patients. Available treatments are symptomatic in nature and are only sufficient to improve the quality of life of AD patients temporarily. A potential strategy, currently under investigation, is to target cell-signaling pathways associated with neurodegeneration, in order to decrease neuroinflammation, excitotoxicity, and to improve cognitive functions. Current review centers on the role of neuroinflammation and the specific contribution of mast cells to AD pathophysiology...
June 2015: Expert Review of Neurotherapeutics
Chunyun Huang, Youyu Sheng, Jack Jia, Lianjun Chen
BACKGROUND: Melanoma is a leading cause of cancer death. Thus, accurate prognostic biomarkers that will assist rational treatment planning need to be identified. METHODS: Microarray analysis of melanoma and normal tissue samples was performed to identify differentially expressed modules (DEMs) from the signaling network and ultimately detect molecular markers to support histological examination. Network motifs were extracted from the human signaling network. Then, significant expression-correlation differential modules were identified by comparing the network module expression-correlation differential scores under normal and disease conditions using the gene expression datasets...
November 2014: Journal of Cancer Research and Therapeutics
Frédérique Végran, Hélène Berger, Romain Boidot, Grégoire Mignot, Mélanie Bruchard, Magalie Dosset, Fanny Chalmin, Cédric Rébé, Valentin Dérangère, Bernhard Ryffel, Masashi Kato, Armelle Prévost-Blondel, François Ghiringhelli, Lionel Apetoh
The TH9 subset of helper T cells was initially shown to contribute to the induction of autoimmune and allergic diseases, but subsequent evidence has suggested that these cells also exert antitumor activities. However, the molecular events that account for their effector properties are elusive. Here we found that the transcription factor IRF1 enhanced the effector function of TH9 cells and dictated their anticancer properties. Under TH9-skewing conditions, interleukin 1β (IL-1β) induced phosphorylation of the transcription factor STAT1 and subsequent expression of IRF1, which bound to the promoters of Il9 and Il21 and enhanced secretion of the cytokines IL-9 and IL-21 from TH9 cells...
August 2014: Nature Immunology
Yuanyuan Zhang, Yong Yang, Lei Chen, Jianhong Zhang
BACKGROUND: Uveal melanoma is an aggressive cancer which has a high percentage metastasizing to the liver, with a worse prognosis. Identification of patients at high risk of metastases may provide information for early detection of metastases and treatment. METHODS: Expression profiling of ocular tumor tissues from 46 liver metastatic uveal melanoma samples and 45 non-metastatic uveal melanoma samples were got from GEO database. Bioinformatic analyses such as the Gene Oncology and Kyoto Encyclopedia of Genes and Genomes were used to identify genes and pathways specifically associated with liver metastases of the uveal melanoma...
2014: BMC Medical Genetics
Guillermina Yanek Jiménez-Andrade, Alfredo Ibarra-Sánchez, Diana González, Mónica Lamas, Claudia González-Espinosa
BACKGROUND: High concentrations of plasmatic IgE have been related to distinct systemic inflammatory conditions that frequently predispose individuals to hypersensitivity reactions. Although effects of IgE have been suggested to relay on the low-intensity activation of distinct effector elements of the immune system, such as mast cells (MC), experimental evidence on the role of IgE-induced production of inflammatory mediators on specific pathologies is scarce. MC are an important component in tumor microenvironment where they seem to secrete a number of immunomodulatory and angiogenic mediators, such as the Vascular Endothelial Growth Factor (VEGF) by not well-described mechanisms...
2013: Journal of Hematology & Oncology
Laura Nousiainen, Maarit Sillanpää, Miao Jiang, James Thompson, Jussi Taipale, Ilkka Julkunen
Activation of host innate antiviral responses are mediated by retinoic-acid inducible gene I (RIG-I)-like receptors, RIG-I and melanoma differentiation-associated gene 5, and TLRs 3, 7, 8 and 9, recognising different types of viral nucleic acids. The major components of the RIG-I- and TLR pathways have putatively been identified, but previously unrecognised kinases may contribute to virus infection-induced activation of the IFN response. Here, we screened a human kinase cDNA library, termed the kinome, using an IFN-λ1 promoter-driven luciferase reporter assay in HEK293 cells during Sendai virus infection...
October 2013: Innate Immunity
Zhongjun Dong, Dominique Davidson, Luis Alberto Pérez-Quintero, Tomohiro Kurosaki, Wojciech Swat, André Veillette
The adaptor SAP, mutated in X-linked lymphoproliferative disease, has critical roles in multiple immune cell types. Among these, SAP is essential for the ability of natural killer (NK) cells to eliminate abnormal hematopoietic cells. Herein, we elucidated the molecular and cellular bases of this activity. SAP enhanced NK cell responsiveness by a dual molecular mechanism. It coupled SLAM family receptors to the kinase Fyn, which triggered the exchange factor Vav-1 and augmented NK cell activation. SAP also prevented the inhibitory function of SLAM family receptors...
June 29, 2012: Immunity
Lisa C Neumann, Andreas Weinhäusel, Stefanie Thomas, Bernhard Horsthemke, Dietmar R Lohmann, Michael Zeschnigk
BACKGROUND: Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed EFS (embryonal Fyn-associated substrate) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated EFS promoter region CpG island in tumor classification and metastatic progression...
2011: BMC Cancer
Delphine Lamoral-Theys, Nathalie Wauthoz, Petra Heffeter, Véronique Mathieu, Utte Jungwirth, Florence Lefranc, Jean Nève, Jacques Dubois, François Dufrasne, Karim Amighi, Walter Berger, Philippe Gailly, Robert Kiss
Cancer cells exhibit de-regulation of multiple cellular signalling pathways and treatments of various types of cancers with polyphenols are promising. We recently reported the synthesis of a series of 33 novel divanillic and trivanillic polyphenols that displayed anticancer activity, at least in vitro, through inhibiting various kinases. This study revealed that minor chemical modifications of a trivanillate scaffold could convert cytotoxic compounds into cytostatic ones. Compound 13c, a tri-chloro derivative of trivanillic ester, displayed marked inhibitory activities against FGF-, VEGF-, EGF- and Src-related kinases, all of which are implicated not only in angiogenesis but also in the biological aggressiveness of various cancer types...
July 2012: Journal of Cellular and Molecular Medicine
Juan Carlos Montero, Samuel Seoane, Alberto Ocaña, Atanasio Pandiella
Dasatinib is a small molecule tyrosine kinase inhibitor that targets a wide variety of tyrosine kinases implicated in the pathophysiology of several neoplasias. Among the most sensitive dasatinib targets are ABL, the SRC family kinases (SRC, LCK, HCK, FYN, YES, FGR, BLK, LYN, and FRK), and the receptor tyrosine kinases c-KIT, platelet-derived growth factor receptor (PDGFR) α and β, discoidin domain receptor 1 (DDR1), c-FMS, and ephrin receptors. Dasatinib inhibits cell duplication, migration, and invasion, and it triggers apoptosis of tumoral cells...
September 1, 2011: Clinical Cancer Research
Harriet M Kluger, Arkadiuz Z Dudek, Carrie McCann, Jean Ritacco, Nadine Southard, Lucia B Jilaveanu, Annette Molinaro, Mario Sznol
BACKGROUND: Inhibiting src kinases (non-receptor tyrosine kinase signaling intermediates) reduces melanoma cell proliferation and invasion. Dasatinib inhibits c-kit, PDGFβR, and EPHA2 and src kinases c-src, c-Yes, Lck, and Fyn. A phase 2 trial of dasatinib in melanoma was conducted to assess response rate (RR), progression-free survival (PFS), and toxicity. METHODS: Adults with stage 3/4 chemotherapy-naïve unresectable melanoma were eligible. Dasatinib was initially administered at 100 mg twice daily continuously to 17 patients...
May 15, 2011: Cancer
Vipin Yadav, Mitchell F Denning
Src family kinases (SFKs) are frequently over-expressed and/or activated in human cancers, and play key roles in cancer cell invasion, metastasis, proliferation, survival, and angiogenesis. Allosteric activation of SFKs occurs through well-defined post-translational mechanisms, however the SFK member Fyn is over-expressed in multiple human cancers (prostate, melanoma, pancreatic, glioma, chronic myelogenous leukemia) and the mechanism of increased Fyn expression is unclear. Since activation of Ras oncogenes is a common oncogenic event leading to the activation of multiple effector pathways, we explored if Ras could induce Fyn expression...
May 2011: Molecular Carcinogenesis
Kazunori Hamamura, Momoko Tsuji, Hiroshi Hotta, Yuki Ohkawa, Masataka Takahashi, Hidenobu Shibuya, Hideyuki Nakashima, Yoshio Yamauchi, Noboru Hashimoto, Hisashi Hattori, Minoru Ueda, Keiko Furukawa, Koichi Furukawa
The possible roles of Src family kinases in the enhanced malignant properties of melanomas related to GD3 expression were analyzed. Among Src family kinases only Yes, not Fyn or Src, was functionally involved in the increased cell proliferation and invasion of GD3-expressing transfectant cells (GD3+). Yes was located upstream of p130Cas and paxillin and at an equivalent level to focal adhesion kinase. Yes underwent autophosphorylation even before serum treatment and showed stronger kinase activity in GD3+ cells than in GD3- cells following serum treatment...
May 27, 2011: Journal of Biological Chemistry
Patrick M Brauer, Angela L Tyner
The Fyn related kinase FRK, originally called RAK, is a member of a small family of intracellular Src-related tyrosine kinases that includes PTK6 and Srms. These kinases share a conserved gene structure that is distinct from that of the Src family. Expression of FRK and PTK6 was originally identified in melanoma, breast cancer cells and normal intestinal epithelium, and both FRK and PTK6 have been implicated in the regulation of epithelial cell differentiation and apoptosis. Recently FRK was reported to phosphorylate the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10), a negative regulator of phosphatidylinositol 3 kinase (PI3K) signaling and AKT activation...
September 1, 2009: Cell Cycle
Janka Teutschbein, Manfred Schartl, Svenja Meierjohann
The Src family kinase/Focal Adhesion Kinase (FAK) complex is a signaling platform playing a crucial role in transformation downstream of oncogenic growth factor receptors. In the case of melanoma in Xiphophorus fish, the oncogenic EGF receptor orthologue Xiphophorus melanoma receptor kinase (Xmrk) effects continuous activation of the Src family kinase Fyn, but not of the other family members Src or Yes. Here, Fyn is strongly involved in promoting many tumorigenic events. Although Fyn is expressed in most mammalian tissues, there are only few reports of its involvement in the development of solid tumors...
March 2009: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Svenja Meierjohann, Elisabeth Wende, Anita Kraiss, Claudia Wellbrock, Manfred Schartl
One of the most prominent features of malignant melanoma is the fast generation of metastasizing cells, resulting in the poor prognosis of patients with this tumor type. For this process, cells must gain the ability to migrate. The oncogenic receptor Xmrk (Xiphophorus melanoma receptor kinase) from the Xiphophorus melanoma system is a mutationally activated version of the epidermal growth factor receptor that induces the malignant transformation of pigment cells. Here, we show that the activation of Xmrk leads to a clear increase of pigment cell motility in a fyn-dependent manner...
March 15, 2006: Cancer Research
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