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Wnt/b-catenin signal

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https://www.readbyqxmd.com/read/28811361/chemoradiotherapy-resistance-in-colorectal-cancer-cells-is-mediated-by-wnt-%C3%AE-catenin-signaling
#1
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/28798691/fentanyl-promotes-breast-cancer-cell-stemness-and-epithelial-mesenchymal-transition-by-upregulating-%C3%AE-1-6-fucosylation-via-wnt-%C3%AE-catenin-signaling-pathway
#2
Hong-Fang Yang, Ming Yu, Hui-Dan Jin, Jia-Qi Yao, Zhi-Li Lu, Iddrisu B Yabasin, Qiu Yan, Qing-Ping Wen
Cancer pain is a common and severe complication of human breast cancer, and relieving pain is fundamental strategy in the treatment. Fentanyl, as an opioid analgesic, is widely used in breast cancer patients. However, little is known about its effects on stemness and epithelial-mesenchymal transition (EMT) of breast cancer cells. Aberrant protein glycosylation is involved in cancer malignancy. The α1, 6-fucosylation is an important type of glycosylation, and the elevated α1, 6-fucosylation catalyzed by fucosyltransferase VIII (FUT8) is found in many tumors...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28783170/loss-of-claudin-3-expression-induces-il6-gp130-stat3-signaling-to-promote-colon-cancer-malignancy-by-hyperactivating-wnt-%C3%AE-catenin-signaling
#3
R Ahmad, B Kumar, Z Chen, X Chen, D Müller, S M Lele, M K Washington, S K Batra, P Dhawan, A B Singh
The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28770967/suppression-of-adriamycin-resistance-in-osteosarcoma-by-blocking-wnt-%C3%AE-catenin-signal-pathway
#4
B-Q Wu, Y Cao, Z-G Bi
OBJECTIVE: Wnt/β-catenin signal pathway plays a role in regulating cell proliferation and apoptosis, and is correlated with tumor onset, progression and drug resistance. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic factor inducing tumor cell drug resistance. Wnt/β-catenin signal pathway can modulate Bcl-2 expression. This study established a cell model of drug resistance using adriamycin (ADM) treatment. Wnt/β-catenin signal pathway was intervened to discuss its role in drug resistance of osteosarcoma cells...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28767428/suppression-of-mir-708-inhibits-the-wnt-%C3%AE-catenin-signaling-pathway-by-activating-dkk3-in-adult-b-all
#5
Yingjie Zhang, Huibo Li, Rongyi Cao, Lili Sun, Yan Wang, Shengjin Fan, Yanqiu Zhao, Desheng Kong, Lin Cui, Leilei Lin, Ke Wang, Yinghua Li, Jin Zhou
Inactivation of Dickkopf-3 (DKK3) is closely associated with a poor prognosis in various solid tumor and hematologic malignancies. Promoter hypermethylation is one potential cause of DKK3 inactivation. However, whether other mechanisms lead to DKK3 inactivation and the subsequent effects of these inactivations on cell proliferation and the Wnt signaling pathway in adult B acute lymphoblastic leukemia (B-ALL) remain unclear. In the present study, we found that low DKK3 expression levels were associated with high miR-708 expression and promoter hypermethylation in adult B-ALL...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751540/ttk-inhibitors-as-a-targeted-therapy-for-ctnnb1-%C3%AE-catenin-mutant-cancers
#6
Guido J R Zaman, Jeroen A D M de Roos, Marion A A Libouban, Martine B W Prinsen, Jos de Man, Rogier C Buijsman, Joost C M Uitdehaag
The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of chromosome segregation and is the subject of novel targeted therapy approaches by small molecule inhibitors. While the first TTK inhibitors have entered phase 1 dose escalating studies in combination with taxane chemotherapy, a patient stratification strategy is still missing. With the aim to identify a genomic biomarker to predict the response of tumor cells to TTK inhibitor therapy, we profiled a set of pre-clinical and clinical TTK inhibitors from different chemical series on a panel of sixty-six genetically characterized cell lines derived from different tumors (Oncolines)...
July 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28747340/epithelial-tnf-receptor-signaling-promotes-mucosal-repair-in-inflammatory-bowel-disease
#7
Emily M Bradford, Stacy H Ryu, Ajay Pal Singh, Goo Lee, Tatiana Goretsky, Preetika Sinh, David B Williams, Amber L Cloud, Elias Gounaris, Vihang Patel, Olivia F Lamping, Evan B Lynch, Mary Pat Moyer, Isabelle G De Plaen, David J Shealy, Guang-Yu Yang, Terrence A Barrett
TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28743881/wnt-signaling-controls-pro-regenerative-collagen-xii-in-functional-spinal-cord-regeneration-in-zebrafish
#8
Daniel Wehner, Themistoklis M Tsarouchas, Andria Michael, Christa Haase, Gilbert Weidinger, Michell M Reimer, Thomas Becker, Catherina G Becker
The inhibitory extracellular matrix in a spinal lesion site is a major impediment to axonal regeneration in mammals. In contrast, the extracellular matrix in zebrafish allows substantial axon re-growth, leading to recovery of movement. However, little is known about regulation and composition of the growth-promoting extracellular matrix. Here we demonstrate that activity of the Wnt/β-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/β-catenin signaling induces expression of col12a1a/b and deposition of Collagen XII, which is necessary for axons to actively navigate the non-neural lesion site environment...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#9
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28727410/exosomes-mediate-epithelium-mesenchyme-crosstalk-in-organ-development
#10
Nan Jiang, Lusai Xiang, Ling He, Guodong Yang, Jinxuan Zheng, Chenglin Wang, Yimei Zhang, Sainan Wang, Yue Zhou, Tzong-Jen Sheu, Jiaqian Wu, Kenian Chen, Paulo G Coelho, Nicky M Tovar, Shin Hye Kim, Mo Chen, Yan-Heng Zhou, Jeremy J Mao
Organ development requires complex signaling by cells in different tissues. Epithelium and mesenchyme interactions are crucial for the development of skin, hair follicles, kidney, lungs, prostate, major glands, and teeth. Despite myriad literature on cell-cell interactions and ligand-receptor binding, the roles of extracellular vesicles in epithelium-mesenchyme interactions during organogenesis are poorly understood. Here, we discovered that ∼100 nm exosomes were secreted by the epithelium and mesenchyme of a developing tooth organ and diffused through the basement membrane...
July 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28725522/pathogenetic-analysis-of-sinonasal-teratocarcinosarcomas-reveal-actionable-%C3%AE-catenin-overexpression-and-a-%C3%AE-catenin-mutation
#11
Andrew C Birkeland, Sarah J Burgin, Megan Yanik, Megan V Scott, Carol R Bradford, Jonathan B McHugh, Scott A McLean, Stephen E Sullivan, Jacques E Nor, Erin L McKean, J Chad Brenner
Objective  Sinonasal teratocarcinosarcomas are rare, aggressive tumors of the skull base. Treatment options are limited and outcomes are poor. Little is known in regard to the genetic factors regulating these tumors. Characterization of actionable molecular alterations in these tumors could provide potentially successful therapeutic options. Methods  We performed targeted exome sequencing on an index sinonasal teratocarcinosarcoma specimen to identify potential driver mutations. We performed immunohistochemical stains for β-catenin on paraffin-embedded tissue on the index tumor and a subsequent teratocarcinosarcoma...
August 2017: Journal of Neurological Surgery. Part B, Skull Base
https://www.readbyqxmd.com/read/28716029/foxp3-promotes-tumor-growth-and-metastasis-by-activating-wnt-%C3%AE-catenin-signaling-pathway-and-emt-in-non-small-cell-lung-cancer
#12
Shucai Yang, Yi Liu, Ming-Yue Li, Calvin S H Ng, Sheng-Li Yang, Shanshan Wang, Chang Zou, Yujuan Dong, Jing Du, Xiang Long, Li-Zhong Liu, Innes Y P Wan, Tony Mok, Malcolm J Underwood, George G Chen
BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28710530/proteomic-characterisation-reveals-active-wnt-signalling-by-human-multipotent-stromal-cells-as-a-key-regulator-of-beta-cell-survival-and-proliferation
#13
Miljan Kuljanin, Gillian I Bell, Stephen E Sherman, Gilles A Lajoie, David A Hess
AIMS/HYPOTHESIS: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. METHODS: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC(R)) vs nonregenerative (MSC(NR)) capacity...
July 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28708826/intestinal-stem-cell-overproliferation-resulting-from-inactivation-of-the-apc-tumor-suppressor-requires-the-transcription-cofactors-earthbound-and-erect-wing
#14
Ai Tian, Hassina Benchabane, Zhenghan Wang, Chloe Zimmerman, Nan Xin, Jessica Perochon, Gabriela Kalna, Owen J Sansom, Chao Cheng, Julia B Cordero, Yashi Ahmed
Wnt/β-catenin signal transduction directs intestinal stem cell (ISC) proliferation during homeostasis. Hyperactivation of Wnt signaling initiates colorectal cancer, which most frequently results from truncation of the tumor suppressor Adenomatous polyposis coli (APC). The β-catenin-TCF transcription complex activates both the physiological expression of Wnt target genes in the normal intestinal epithelium and their aberrantly increased expression in colorectal tumors. Whether mechanistic differences in the Wnt transcription machinery drive these distinct levels of target gene activation in physiological versus pathological states remains uncertain, but is relevant for the design of new therapeutic strategies...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28703283/wnt-signaling-pathways-in-chronic-lymphocytic-leukemia-and-b-cell-lymphomas
#15
REVIEW
Pavlína Janovská, Vítězslav Bryja
In this review, we discuss the intricate roles of the WNT signaling network in the development and progression of mature B cell-derived hematological malignancies, with a focus on chronic lymphocytic leukemia (CLL) and related B cell lymphomas. We review the current literature and highlight the differences between the β-catenin-dependent and independent branches of WNT signaling. Special attention is paid to the role of the non-canonical WNT/Planar cell polarity (PCP) pathway, mediated by the WNT5-ROR1-Dishevelled (DVL) signaling axis in CLL...
July 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28701516/blocking-tgf-%C3%AE-and-%C3%AE-catenin-epithelial-crosstalk-exacerbates-ckd
#16
Stellor Nlandu-Khodo, Surekha Neelisetty, Melanie Phillips, Marika Manolopoulou, Gautam Bhave, Lauren May, Peter E Clark, Haichun Yang, Agnes B Fogo, Raymond C Harris, M Mark Taketo, Ethan Lee, Leslie S Gewin
The TGF-β and Wnt/β-catenin pathways have important roles in modulating CKD, but how these growth factors affect the epithelial response to CKD is not well studied. TGF-β has strong profibrotic effects, but this pleiotropic factor has many different cellular effects depending on the target cell type. To investigate how TGF-β signaling in the proximal tubule, a key target and mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-β type 2 receptor specifically in this epithelial segment...
July 12, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28685286/modulation-of-wnt-signaling-pathway-by-hepatitis-b-virus
#17
REVIEW
Muhammad Daud, Muhammad Adeel Rana, Tayyab Husnain, Bushra Ijaz
Hepatitis B virus (HBV) has a global distribution and is one of the leading causes of hepatocellular carcinoma. The precise mechanism of pathogenicity of HBV-associated hepatocellular carcinoma (HCC) is not yet fully understood. Viral-related proteins are known to take control of several cellular pathways like Wnt/β-catenin, TGF-β, Raf/MAPK and ROS for the virus's own replication. This affects cellular persistence, multiplication, migration, alteration and genomic instability. The Wnt/FZD/β-catenin signaling pathway plays a significant role in the pathology and physiology of the liver and has been identified as a main factor in HCC development...
July 6, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28677721/zinc-finger-protein-545-is-inactivated-due-to-promoter-methylation-and-functions-as-a-tumor-suppressor-through-the-wnt-%C3%AE-catenin-pi3k-akt-and-mapk-erk-signaling-pathways-in-colorectal-cancer
#18
Shili Xiang, Tingxiu Xiang, Qian Xiao, Yunhai Li, Bianfei Shao, Tao Luo
The transcription factor, zinc-finger protein 545 (ZNF545), that belongs to the Kruppel-associated box zinc-finger protein (KRAB-ZFP) family, acts as a tumor suppressor and is inactivated by promoter methylation in cancers such as nasopharyngeal carcinoma, breast cancer, and gastric cancer, but its role in colorectal cancer (CRC) is unknown. The purpose of this study was to characterize the ZNF545 expression, methylation status, biological function, and related molecular mechanisms in CRC. The results showed that ZNF545 was expressed in adult normal colorectal tissues, but downregulated or silenced in CRC cell lines, and this mechanism was reversed by demethylation treatment with 5-aza-2'-deoxycytidine and trichostatin A...
July 4, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28675177/norrin-induced-frizzled4-endocytosis-and-endo-lysosomal-trafficking-control-retinal-angiogenesis-and-barrier-function
#19
Chi Zhang, Maria B Lai, Lavan Khandan, Lindsey A Lee, Zhe Chen, Harald J Junge
Angiogenesis and blood-brain barrier formation are required for normal central nervous system (CNS) function. Both processes are controlled by Wnt or Norrin (NDP) ligands, Frizzled (FZD) receptors, and β-catenin-dependent signalling in vascular endothelial cells. In the retina, FZD4 and the ligand NDP are critical mediators of signalling and are mutated in familial exudative vitreoretinopathy. Here, we report that NDP is a potent trigger of FZD4 ubiquitination and induces internalization of the NDP receptor complex into the endo-lysosomal compartment...
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28671671/wnt-%C3%AE-catenin-activation-and-macrophage-induction-during-liver-cancer-development-following-steatosis
#20
A Debebe, V Medina, C-Y Chen, I M Mahajan, C Jia, D Fu, L He, N Zeng, B W Stiles, C-L Chen, M Wang, K-R Aggarwal, Z Peng, J Huang, J Chen, M Li, T Dong, S Atkins, Z Borok, W Yuan, K Machida, C Ju, M Kahn, D Johnson, B L Stiles
Obesity confers an independent risk for carcinogenesis. In the liver, steatosis often proceeds cancer formation; however, the mechanisms by which steatosis promotes carcinogenesis is unknown. We hypothesize that steatosis alters the microenvironment to promote proliferation of tumor initiating cells (TICs) and carcinogenesis. We used several liver cancer models to address the mechanisms underlying the role of obesity in cancer and verified these findings in patient populations. Using bioinformatics analysis and verified by biochemical assays, we identified that hepatosteatosis resulting from either Pten deletion or transgenic expression of HCV core/NS5A proteins, promotes the activation of Wnt/β-catenin...
July 3, 2017: Oncogene
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