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Wnt beta catenin

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https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#1
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28223363/auto-inhibition-of-dishevelled-regulated-by-its-extreme-c-terminus-plays-a-distinct-role-in-wnt-beta-catenin-and-wnt-pcp-signaling-pathways
#2
Jing Qi, Ho-Jin Lee, Audrey Saquet, Xiao-Ning Cheng, Ming Shao, Jie J Zheng, De-Li Shi
Dishevelled (Dvl) is a key intracellular signaling molecule that mediates the activation of divergent Wnt pathways. It contains three highly conserved domains known as DIX, PDZ and DEP, whose functions in beta-catenin-dependent canonical Wnt and beta-catenin-independent non-canonical Wnt signaling have been well characterized. The C-terminal region is also highly conserved from invertebrates to vertebrates. However, its function in regulating the activation of different Wnt signals remains unclear. We previously reported that Dvl conformational change triggered by the highly conserved PDZ-binding C-terminus is important for the pathway specificity...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28217097/feedback-activation-of-basic-fibroblast-growth-factor-signaling-via-the-wnt-%C3%AE-catenin-pathway-in-skin-fibroblasts
#3
Xu Wang, Yuting Zhu, Congcong Sun, Tao Wang, Yingjie Shen, Wanhui Cai, Jia Sun, Lisha Chi, Haijun Wang, Na Song, Chao Niu, Jiayi Shen, Weitao Cong, Zhongxin Zhu, Yuanhu Xuan, Xiaokun Li, Litai Jin
Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28191283/active-%C3%AE-catenin-is-regulated-by-the-pten-pi3-kinase-pathway-a-role-for-protein-phosphatase-pp2a
#4
Amit Persad, Geetha Venkateswaran, Li Hao, Maria E Garcia, Jenny Yoon, Jaskiran Sidhu, Sujata Persad
Dysregulation of Wnt/β-catenin signaling has been associated with the development and progression of many cancers. The stability and subcellular localization of β-catenin, a dual functional protein that plays a role in intracellular adhesion and in regulating gene expression, is tightly regulated. However, little is known about the transcriptionally active form of β-catenin, Active Beta Catenin (ABC), that is unphosphorylated at serine 37 (Ser37) and threonine 41 (Thr41). Elucidating the mechanism by which β-catenin is activated to generate ABC is vital to the development of therapeutic strategies to block β-catenin signaling for cancer treatment...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28186678/gamma-secretase-inhibitor-ix-gsi-impairs-concomitant-activation-of-notch-and-wnt-beta-catenin-pathways-in-cd44-gastric-cancer-stem-cells
#5
Samarpita Barat, Xi Chen, Khac Cuong Bui, Przemyslaw Bozko, Julian Götze, Matthias Christgen, Till Krech, Nisar P Malek, Ruben R Plentz
Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44(+) CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment...
February 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28152305/concurrent-hypermethylation-of-sfrp2-and-dkk2-activates-the-wnt-%C3%AE-catenin-pathway-and-is-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#6
Hao Wang, Xiang-Long Duan, Xiao-Li Qi, Lei Meng, Yi-Song Xu, Tong Wu, Peng-Gao Dai
Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28143772/stearoyl-coa-desaturase-promotes-liver-fibrosis-and-tumor-development-in-mice-via-a-wnt-positive-signaling-loop-by-stabilization-of-low-density-lipoprotein-receptor-related-proteins-5-and-6
#7
Keane K Y Lai, Soo-Mi Kweon, Feng Chi, Edward Hwang, Yasuaki Kabe, Reiichi Higashiyama, Lan Qin, Rui Yan, Raymond P Wu, Naoaki Fujii, Samuel French, Jun Xu, Jian-Ying Wang, Ramanchadran Murali, Lopa Mishra, Ju-Seog Lee, James M Ntambi, Hidekazu Tsukamoto
BACKGROUND & AIMS: Stearoyl-CoA desaturase (SCD) synthesizes monounsaturated fatty acids (MUFAs) and has been associated with development of metabolic syndrome, tumorigenesis, and stem cell characteristics. We investigated whether and how SCD promotes liver fibrosis and tumor development in mice. METHODS: Rodent primary hepatic stellate cells (HSCs), mouse liver tumor-initiating stem cell-like cells (TICs), and human hepatocellular carcinoma (HCC) cell lines were exposed to Wnt signaling inhibitors and changes in gene expression patterns were analyzed...
January 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28123643/gsk3%C3%AE-activity-is-essential-for-senescence-associated-heterochromatin-foci-sahf-formation-induced-by-hmga2-in-wi38-cells
#8
Xi Shi, Baoqing Tian, Chi Ma, Lingxia Liu, Na Zhang, Yuan Na, Jing Li, Jun Lu, Yuehua Qiao
Cellular senescence is an irreversible form of cell cycle arrest, which is often characterized by domains of facultative heterochromatin substructures also known as senescence-associated heterochromatin foci (SAHF). SAHF assembly is likely mediated through the downregulation of the Wnt pathway, which inhibits Glycogen Synthase Kinase 3 Beta (GSK3β) in cells undergoing replicative senescence. Alternatively, High Mobility Group AT-Hook 2 (HMGA2) can also induce SAHF formation in primary cells, through a process in which the involved cell signaling pathway is unknown...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28119087/rap1b-a-dvl2-binding-protein-activates-wnt-beta-catenin-signaling-in-esophageal-squamous-cell-carcinoma
#9
Zhao Jia, Yang Yang, Zhu Dengyan, Zhang Chunyang, Liu Donglei, Wu Kai, Zhao Song
RAP1B is a small GTPase, which regulates multiple cellular processes. Up-regulation of RAP1B has been observed in several cancer types. Although previous study has shown that miR-518 inhibited the proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells possibly by targeting RAP1B, the expression pattern and the functions of RAP1B in ESCC are not fully understood. Here, we have fund that the expression of RAP1B was up-regulated in ESCC clinical samples. Gain-of-function and loss-of-function assays demonstrated that RAP1B promoted the growth, migration and metastasis of the ESCC cells...
January 21, 2017: Gene
https://www.readbyqxmd.com/read/28100625/the-ptpn14-tumour-suppressor-is-a-degradation-target-of-human-papillomavirus-e7
#10
Anita Szalmás, Vjekoslav Tomaić, Om Basukala, Paola Massimi, Suruchi Mittal, József Kónya, Lawrence Banks
: Activation of signalling pathways ensuring cell growth are essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumour suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signalling pathways. In this study we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#11
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28054444/heterozygous-pathogenic-variant-in-dact1-causes-an-autosomal-dominant-syndrome-with-features-overlapping-townes-brocks-syndrome
#12
Bryn D Webb, Sanjeeva Metikala, Patricia G Wheeler, Mingma D Sherpa, Sander M Houten, Marko E Horb, Eric E Schadt
A heterozygous nonsense variant was identified in dapper, antagonist of beta-catenin, 1 (DACT1) via whole-exome sequencing in family members with imperforate anus, structural renal abnormalities, genitourinary anomalies, and/or ear anomalies. The DACT1 c.1256G>A;p.Trp419(*) variant segregated appropriately in the family consistent with an autosomal dominant mode of inheritance. DACT1 is a member of the Wnt-signaling pathway, and mice homozygous for null alleles display multiple congenital anomalies including absent anus with blind-ending colon and genitourinary malformations...
January 5, 2017: Human Mutation
https://www.readbyqxmd.com/read/28043904/liver-cancer-cell-of-origin-molecular-class-and-effects-on%C3%A2-patient-prognosis
#13
REVIEW
Daniela Sia, Augusto Villanueva, Scott L Friedman, Josep M Llovet
Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis and clarify the classes of liver cancer based on molecular features and how they affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis...
December 30, 2016: Gastroenterology
https://www.readbyqxmd.com/read/28028178/c-flipl-modulated-wnt-%C3%AE-catenin-activation-via-association-with-tip49-protein
#14
Jing Zhang, Heng-Yi Jiang, Lin-Kai Zhang, Wen-Ling Xu, Yi-Ting Qiao, Xu-Guo Zhu, Wan Liu, Qian-Qian Zheng, Zi-Chun Hua
Cellular FLICE-like inhibitory protein (c-FLIPL) is a key inhibitory protein in the extrinsic apoptotic pathway. Recent studies showed that c-FLIPL could translocate into the nucleus and might be involved in the Wnt signaling pathway. The nuclear function of c-FLIPL was still unclear. Here we found a novel c-FLIPL-associated protein TIP49, which is a nuclear protein identified as a cofactor in the transcriptional regulation of β-catenin. They had co-localization in the nucleus and the DED domain of c-FLIPL was required for the association with TIP49...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28012864/germline-and-somatic-dicer1-mutations-in-familial-and-sporadic-liver-tumors
#15
Stefano Caruso, Julien Calderaro, Eric Letouzé, Jean-Charles Nault, Gabrielle Couchy, Anais Boulais, Alain Luciani, Elie-Serge Zafrani, Paulette Bioulac-Sage, Olivier Seror, Sandrine Imbeaud, Jessica Zucman-Rossi
BACKGROUND & AIMS: Growing evidence suggests that genetic predisposition significantly increases the risk of hepatocellular carcinoma (HCC), independently from the presence of other risk factors. Here, we report a novel germline DICER1 mutation associated with familial recurrent liver tumors. Next, we aimed to investigate the contribution of constitutional and somatic DICER1 mutations on HCC occurrence. METHODS: We investigated two individuals of a family that developed recurrent well-differentiated hepatocellular tumors over the years...
December 21, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27999207/roles-of-gsk-3-and-micrornas-on-epithelial-mesenchymal-transition-and-cancer-stem-cells
#16
REVIEW
James A McCubrey, Timothy L Fitzgerald, Li V Yang, Kvin Lertpiriyapong, Linda S Steelman, Stephen L Abrams, Giuseppe Montalto, Melchiorre Cervello, Luca M Neri, Lucio Cocco, Alberto M Martelli, Piotr Laidler, Joanna DuliÅ Ska-Litewka, Dariusz Rakus, Agnieszka Gizak, Ferdinando Nicoletti, Luca Falzone, Saverio Candido, Massimo Libra
Various signaling pathways exert critical roles in the epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). The Wnt/beta-catenin, PI3K/PTEN/Akt/mTORC, Ras/Raf/MEK/ERK, hedgehog (Hh), Notch and TP53 pathways elicit essential regulatory influences on cancer initiation, EMT and progression. A common kinase involved in all these pathways is moon-lighting kinase glycogen synthase kinase-3 (GSK-3). These pathways are also regulated by micro-RNAs (miRs). TP53 and components of these pathways can regulate the expression of miRs...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27938502/novel-advances-in-understanding-of-molecular-pathogenesis-of-hepatoblastoma-a-wnt-%C3%AE-catenin-perspective
#17
Danielle Bell, Sarangarajan Ranganathan, Junyan Tao, Satdarshan P Monga
Hepatoblastoma is the most common pediatric liver malignancy, typically striking children within the first 3 years of their young lives. While advances in chemotherapy and newer surgical techniques have improved survival in patients with localized disease, unfortunately, for the 25% of patients with metastasis, the overall survival remains poor. These tumors, which are thought to arise from hepatic progenitors or hepatoblasts, hence the name hepatoblastoma, can be categorized by histological subtyping based on their level of cell differentiation...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27907035/exendin-4-inhibits-hepatic-lipogenesis-by-increasing-%C3%AE-catenin-signaling
#18
Mi Hae Seo, Jinmi Lee, Seok-Woo Hong, Eun-Jung Rhee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Won-Young Lee
The aim of this study is to investigate whether the beneficial effect of exendin-4 on hepatic steatosis is mediated by β-catenin signaling. After the HepG2 human hepatoma cells were treated with PA for 24 hours, total triglycerides levels were increased in a dose-dependent manner, and the expression levels of perilipin family members were upregulated in cells treated with 400 μM PA. For our in vitro model of hepatic steatosis, HepG2 cells were treated with 400 μM palmitic acid (PA) in the presence or absence of 100 nM exendin-4 for 24 hours...
2016: PloS One
https://www.readbyqxmd.com/read/27903708/astrocyte-elevated-gene-1-regulates-%C3%AE-catenin-signaling-to-maintain-glioma-stem-like-stemness-and-self-renewal
#19
Bin Hu, Luni Emdad, Timothy P Kegelman, Xue-Ning Shen, Swadesh K Das, Devanand Sarkar, Paul B Fisher
: Glioblastoma multiforme is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSC) are responsible for glioblastoma multiforme escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers, including glioblastoma multiforme, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology...
November 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#20
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
January 10, 2017: Oncotarget
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