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https://www.readbyqxmd.com/read/28812551/the-developmental-basis-for-the-recurrent-evolution-of-deuterostomy-and-protostomy
#1
José M Martín-Durán, Yale J Passamaneck, Mark Q Martindale, Andreas Hejnol
The mouth opening of bilaterian animals develops either separate from (deuterostomy) or connected to (protostomy) the embryonic blastopore, the site of endomesoderm internalization. Although this distinction preluded the classification of bilaterian animals in Deuterostomia and Protostomia, and has influenced major scenarios of bilaterian evolution, the developmental basis for the appearance of these different embryonic patterns remains unclear. To identify the underlying mechanisms, we compared the development of two brachiopod species that show deuterostomy (Novocrania anomala) and protostomy (Terebratalia transversa), respectively...
December 5, 2016: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812103/re-expression-of-pro-fibrotic-embryonic-preserved-mediators-in-irradiated-arterial-vessels-of-the-head-and-neck-region
#2
Patrick Möbius, Raimund H M Preidl, Manuel Weber, Kerstin Amann, Friedrich W Neukam, Falk Wehrhan
PURPOSE: Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling...
August 15, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28811640/a-reciprocal-interaction-between-%C3%AE-catenin-and-osterix-in-cementogenesis
#3
Hwajung Choi, Tak-Heun Kim, Siqin Yang, Jeong-Chae Lee, Hyung-Keun You, Eui-Sic Cho
Although accumulating evidence indicates that both β-catenin and osterix (Osx) are essential for bone and tooth development, few studies have investigated the interaction of these two key proteins in the context of cementogenesis. In this study, we used transgenic mice with constitutively active β-catenin and inactive Osx in the dental mesenchyme to address this question. We found that cementoblasts with constitutively active β-catenin require Osx to produce excessive cellular cementum, and that ablation of Osx prevents this abnormal accumulation...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#4
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811361/chemoradiotherapy-resistance-in-colorectal-cancer-cells-is-mediated-by-wnt-%C3%AE-catenin-signaling
#5
Georg Emons, Melanie Spitzner, Sebastian Reineke, Janneke Möller, Noam Auslander, Frank Kramer, Yue Hu, Tim Beissbarth, Hendrik A Wolff, Margret Rave-Fränk, Elisabeth Heßmann, Jochen Gaedcke, B Michael Ghadimi, Steven Johnsen, Thomas Ried, Marian Grade
Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy (CRT) and TCF7L2 mediates resistance to CRT. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small molecule inhibitor (XAV-939) resulted in sensitization of CRC cells to CRT...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28811300/epigenetic-regulation-by-the-menin-pathway
#6
Zijie Feng, Jian Ma, Xianxin Hua
There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulating several important signaling pathways by controlling gene transcription...
August 15, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28811218/wnt-signaling-positively-regulates-endothelial-cell-fate-specification-in-the-fli1a-positive-progenitor-population-via-lef1
#7
Kathleen Hübner, Kathrin S Grassme, Jyoti Rao, Nina K Wenke, Cordula L Zimmer, Laura Korte, Katja Mu Ller, Saulius Sumanas, Boris Greber, Wiebke Herzog
During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2BAC:Venus-Pest)(mu288); Tg(14TCF:loxP-STOP-loxP-dGFP)(mu202))...
August 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28810936/lncrna-c2dat1-promotes-cell-proliferation-migration-and-invasion-by-targeting-mir-34a-5p-in-osteosarcoma-cells
#8
Daofu Jia, Yanping Niu, Dongling Li, Zhaorui Liu
Osteosarcoma is a highly aggressive malignant bone tumor with poor prognosis in cases. Evidence suggested that lncRNAsare deregulated in multiple cancers. In this study, we investigated the role of the lncRNA C2dat1 on the biological functions of osteosarcoma cells. The expressions of C2dat1, miR-34a-5p and Sirt1 in human osteosarcoma cells were altered by transfection with their specific vectors/shRNA, or mimic/inhibitor. Then, cell viability, migration, invasion and apoptosis were respectively assessed post-transfection...
August 15, 2017: Oncology Research
https://www.readbyqxmd.com/read/28810742/determination-of-rate-limiting-factor-for-formation-of-beta-catenin-destruction-complexes-using-absolute-protein-quantification
#9
Masashi Kitazawa, Tomohisa Hatta, Koji Ogawa, Eriko Fukuda, Naoki Goshima, Tohru Natsume
Wnt/β-catenin signaling plays important roles in both ontogenesis and development. In the absence of a Wnt stimulus, β-catenin is degraded by a multiprotein "destruction complex" that includes Axin, APC, GSK3B, and FBXW11. Although the key molecules required for transducing Wnt signals have been identified, a quantitative understanding of this pathway has been lacking. Here, we calculated the absolute number of β-catenin destruction complexes by absolute protein quantification using LC-MS/MS. Similar amounts of destruction complex-constituting proteins and β-catenin interacted, and the number of destruction complexes was calculated to be about 1,468 molecules/cell...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28810055/impact-of-mir-26b-on-cardiomyocyte-differentiation-in-p19-cells-through-regulating-canonical-non-canonical-wnt-signalling
#10
Duo Wang, Chang Liu, Yumei Wang, Wenjing Wang, Kang Wang, Xiujuan Wu, Zhigang Li, Cuimei Zhao, Li Li, Luying Peng
BACKGROUND AND OBJECTIVES: The control of cardiomyocyte differentiation is tightly linked to microRNAs (miRNAs), which have been emerging as important players in heart development. However, the regulation mechanisms mediated by miRNAs in early heart development remains speculative. Here, we evaluated the impact of miR-26b during the progression of cardiomyocyte differentiation from the P19 cell line. MATERIALS AND METHODS: The overexpression of miR-26b in P19 cells was performed by transduction with lentivirus vector...
August 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28808993/multiplexed-liquid-chromatography-multiple-reaction-monitoring-mass-spectrometry-quantification-of-cancer-signaling-proteins
#11
Yi Chen, Kate J Fisher, Mark Lloyd, Elizabeth R Wood, Domenico Coppola, Erin Siegel, David Shibata, Yian A Chen, John M Koomen
Quantitative evaluation of protein expression across multiple cancer-related signaling pathways (e.g., Wnt/β-catenin, TGF-β, receptor tyrosine kinases (RTK), MAP kinases, NF-κB, and apoptosis) in tumor tissues may enable the development of a molecular profile for each individual tumor that can aid in the selection of appropriate targeted cancer therapies. Here, we describe the development of a broadly applicable protocol to develop and implement quantitative mass spectrometry assays using cell line models and frozen tissue specimens from colon cancer patients...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808893/epigenetics-and-bone-remodeling
#12
REVIEW
Ali Husain, Matlock A Jeffries
PURPOSE OF REVIEW: Bone remodeling is a diverse field of study with many direct clinical applications; past studies have implicated epigenetic alterations as key factors of both normal bone tissue development and function and diseases of pathologic bone remodeling. The purpose of this article is to review the most important recent advances that link epigenetic changes to the bone remodeling field. RECENT FINDINGS: Epigenetics describes three major phenomena: DNA modification via methylation, histone side chain modifications, and short non-coding RNA sequences which work in concert to regulate gene transcription in a heritable fashion...
August 14, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28808228/loss-of-usp9x-disrupts-cell-adhesion-and-components-of-the-wnt-and-notch-signaling-pathways-in-neural-progenitors
#13
Susitha Premarathne, Mariyam Murtaza, Nicholas Matigian, Lachlan A Jolly, Stephen A Wood
Development of neural progenitors depends upon the coordination of appropriate intrinsic responses to extrinsic signalling pathways. Here we show the deubiquitylating enzyme, Usp9x regulates components of both intrinsic and extrinsic fate determinants. Nestin-cre mediated ablation of Usp9x from embryonic neural progenitors in vivo resulted in a transient disruption of cell adhesion and apical-basal polarity and, an increased number and ectopic localisation of intermediate neural progenitors. In contrast to other adhesion and polarity proteins, levels of β-catenin protein, especially S33/S37/T41 phospho-β-catenin, were markedly increased in Usp9x (-/Y) embryonic cortices...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#14
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808213/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#15
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808056/the-crystal-structure-of-full-length-sizzled-from-xenopus-laevis-yields-insights-into-wnt-antagonistic-function-of-secreted-frizzled-related-proteins
#16
Qixin Bu, Zhiqiang Li, Junying Zhang, Fei Xu, Jianmei Liu, Heli Liu
The Wnt signaling pathway is crucial to cell proliferation, differentiation and migration. The secreted frizzled-related proteins (sFRPs) represent the largest family of secreted Wnt inhibitors. However, their function in antagonizing Wnt signaling has remained somewhat controversial. Here we report the crystal structure of Sizzled from Xenopus laevis, the first full-length structure of an sFRP. Tethered by an inter-domain disulfide bond and a linker, the N-terminal CRD domain and the C-terminal NTR domain of Sizzled are arranged in a tandem fashion, with the NTR domain occluding the groove of CRD for Wnt accessibility...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808027/de-novo-mutations-in-inhibitors-of-wnt-bmp-and-ras-erk-signaling-pathways-in-non-syndromic-midline-craniosynostosis
#17
Andrew T Timberlake, Charuta G Furey, Jungmin Choi, Carol Nelson-Williams, Erin Loring, Amy Galm, Kristopher T Kahle, Derek M Steinbacher, Dawid Larysz, John A Persing, Richard P Lifton
Non-syndromic craniosynostosis (NSC) is a frequent congenital malformation in which one or more cranial sutures fuse prematurely. Mutations causing rare syndromic craniosynostoses in humans and engineered mouse models commonly increase signaling of the Wnt, bone morphogenetic protein (BMP), or Ras/ERK pathways, converging on shared nuclear targets that promote bone formation. In contrast, the genetics of NSC is largely unexplored. More than 95% of NSC is sporadic, suggesting a role for de novo mutations. Exome sequencing of 291 parent-offspring trios with midline NSC revealed 15 probands with heterozygous damaging de novo mutations in 12 negative regulators of Wnt, BMP, and Ras/ERK signaling (10...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807725/the-rnf146-e3-ubiquitin-ligase-is-required-for-the-control-of-wnt-signaling-and-body-pattern-formation-in-xenopus
#18
Xuechen Zhu, Rui Xing, Renbo Tan, Rongyang Dai, Qinghua Tao
The RING finger protein Rnf146 encodes an E3 ubiquitin ligase capable of targeting poly-ADP-ribosylated substrates for proteasomal degradation. Rnf146 has been identified as a critical regulator of Axin1 and thus of Wnt/β-catenin signaling. However its physiological significance in vertebrate embryonic development remains to be demonstrated. In this study, we take advantages of early Xenopus embryos to demonstrate that Rnf146 is essential for embryonic pattern formation. Depletion of zygotic Rnf146 using a translation blocking morpholino oligo (MO) results in anteriorized development and increased expression the anterior marker gene Otx2, consistent the notion that Rnf146 is a positive regulator of Wnt/β-catenin signaling through negatively regulating Axin1 expression...
August 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28807667/inhibition-of-beta-catenin-signaling-in-the-skin-rescues-cutaneous-adipogenesis-in-systemic-sclerosis-a-randomized-double-blind-placebo-controlled-trial-of-c-82
#19
Robert Lafyatis, Julio C Mantero, Jessica Gordon, Nina Kishore, Mary Carns, Howard Dittrich, Robert Spiera, Robert W Simms, John Varga
Several studies have suggested that Wnts might contribute to skin fibrosis in systemic sclerosis (SSc) by affecting the differentiation of pluripotent dermal cells. We tested C-82, a therapeutic that inhibits canonical Wnt signaling by blocking the interaction of cAMP Response Element-Binding Protein with β-Catenin and inhibiting Wnt-activated genes. We utilized previously unreported trial design, formulating C-82 for topical application and conducting a placebo controlled, double-blinded clinical trial in which patients with diffuse cutaneous SSc were treated with C-82 or placebo on opposite forearms...
August 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28807594/thyroid-hormone-receptor-beta-agonist-gc-1-inhibits-met-%C3%AE-catenin-driven-hepatocellular-cancer
#20
Elisabetta Puliga, Qian Min, Junyan Tao, Rong Zhang, Tirthadipa Pradhan-Sundd, Minakshi Poddar, Sucha Singh, Amedeo Columbano, Jinming Yu, Satdarshan P Monga
The thyromimetic agent GC-1 induces hepatocyte proliferation via Wnt/β-catenin signaling and may promoting regeneration in both acute and chronic liver insufficiencies. However, β-catenin activation particularly due to mutations in CTNNB1 is seen in a subset of hepatocellular carcinomas (HCC). Thus, it will be critical to address any effect of GC-1 on HCC growth and development, before its use can be advocated to stimulate regeneration in chronic liver diseases. In the current study, we first examine the effect of GC-1 on β-catenin-TCF4 activity in HCC cell lines harboring wild-type or mutated-CTNNB1...
August 11, 2017: American Journal of Pathology
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