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Wnt activators

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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/28230774/inhibition-of-ccar1-a-coactivator-of-%C3%AE-catenin-suppresses-the-proliferation-and-migration-of-gastric-cancer-cells
#2
Te-Sheng Chang, Kuo-Liang Wei, Chung-Kuang Lu, Yi-Hsing Chen, Ying-Tung Cheng, Shui-Yi Tung, Cheng-Shyong Wu, Ming-Ko Chiang
The aberrant activation of Wnt signaling has been implicated in a variety of human cancers, including gastric cancer. Given the current hypothesis that cancer arises from cancer stem cells (CSCs), targeting the critical signaling pathways that support CSC self-renewal appears to be a useful approach for cancer therapy. Cell cycle and apoptosis regulator 1 (CCAR1) is a transcriptional coactivator which has been shown to be a component of Wnt/β-catenin signaling, and which plays an important role in transcriptional regulation by β-catenin...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230291/therapeutic-potentials-of-bdnf-trkb-in-breast-cancer-current-status-and-perspectives
#3
Amir Tajbakhsh, Amin Mokhtari-Zaer, Mehdi Rezaee, Fahimeh Afzaljavan, Mehdi Rivandi, Seyed Mahdi Hassanian, Gordon A Ferns, Alireza Pasdar, Amir Avan
Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB and the p75(NTR) death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#4
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28228258/clonal-expansion-of-lgr5-positive-cells-from-mammalian-cochlea-and-high-purity-generation-of-sensory-hair-cells
#5
Will J McLean, Xiaolei Yin, Lin Lu, Danielle R Lenz, Dalton McLean, Robert Langer, Jeffrey M Karp, Albert S B Edge
Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28223537/reduced-e-cadherin-facilitates-renal-cell-carcinoma-progression-by-wnt-%C3%AE-catenin-signaling-activation
#6
Xinqi Zhang, Mingxi Yang, Hua Shi, Jianxin Hu, Yuanlin Wang, Zhaolin Sun, Shuxiong Xu
Reduced expression of E-cadherin was observed in renal cell carcinoma (RCC). However, its potential clinical value and correlation with WNT/β-catenin signaling in RCC progression was still unclear. Immunohistochemical staining was performed in RCC tissue microarray to examine the expression status and prognosis value of E-cadherin and β-catenin. The potential role of E-cadherin in β-catenin translocation was analyzed with immunobloting assays. A significant negative correlation was observed between E-cadherin and β-catenin expression in RCC tissues...
February 15, 2017: Oncotarget
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
#7
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/28222387/baicalein-enhances-the-osteogenic-differentiation-of-human-periodontal-ligament-cells-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#8
Li-Jiao Chen, Bi-Bo Hu, Xin-Lian Shi, Man-Man Ren, Wen-Bin Yu, Sheng-Dan Cen, Rong-Dang Hu, Hui Deng
OBJECTIVE: Periodontium regeneration is one of the most important processes for periodontitis therapy. Human periodontal ligament cells (hPDLCs) play a vital role in the repair and regeneration of periodontal tissues. Our study aimed to investigated the mechanisms underlying the promotion of hPLDCs osteogenic differentiation by baicalein. DESIGN: hPDLCs were obtained from periodontal ligament (PDL) tissues by primary culture. The MTT assay was used to determine the growth curves of hPDLCs treated with different concentrations of baicalein (1...
February 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28222310/circulating-mirna-associated-with-posttraumatic-stress-disorder-in-a-cohort-of-military-combat-veterans
#9
Christiana G Martin, Hyungsuk Kim, Sijung Yun, Whitney Livingston, Joseph Fetta, Vincent Mysliwiec, Tristin Baxter, Jessica M Gill
Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced. PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones...
January 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28222105/stat3-cdc25a-dependent-cell-proliferation-promotes-embryonic-axis-extension-during-zebrafish-gastrulation
#10
Yinzi Liu, Diane S Sepich, Lilianna Solnica-Krezel
Cell proliferation has generally been considered dispensable for anteroposterior extension of embryonic axis during vertebrate gastrulation. Signal transducer and activator of transcription 3 (Stat3), a conserved controller of cell proliferation, survival and regeneration, is associated with human scoliosis, cancer and Hyper IgE Syndrome. Zebrafish Stat3 was proposed to govern convergence and extension gastrulation movements in part by promoting Wnt/Planar Cell Polarity (PCP) signaling, a conserved regulator of mediolaterally polarized cell behaviors...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28220803/tcf7-is-suppressed-by-the-androgen-receptor-via-microrna-1-mediated-downregulation-and-is-involved-in-the-development-of-resistance-to-androgen-deprivation-in-prostate-cancer
#11
M K Siu, W-Y Chen, H-Y Tsai, H-Y Chen, J J Yin, C-L Chen, Y-C Tsai, Y-N Liu
BACKGROUND: Resistance to androgen deprivation therapy (ADT) represents a key step in the malignant progression of prostate cancer, and mutation to androgen receptor (AR) is one major driver to an androgen-independent phenotype. However, alternative oncogenic pathways that bypass AR signaling have emerged as an important mechanism promoting resistance to ADT. It is known that AR activation can prevent the interaction between β-catenin and T cell factor/lymphoid enhancer-binding factor (TCF/LEF) family, inhibiting the Wnt signaling pathway...
February 21, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28220106/synchronization-by-daytime-restricted-food-access-modulates-the-presence-and-subcellular-distribution-of-%C3%AE-catenin-and-its-phosphorylated-forms-in-the-rat-liver
#12
Dalia Luz De Ita-Pérez, Mauricio Díaz-Muñoz
β-catenin, the principal effector of the Wnt pathway, is also one of the cadherin cell adhesion molecules; therefore, it fulfills signaling and structural roles in most of the tissues and organs. It has been reported that β-catenin in the liver regulates metabolic responses such as gluconeogenesis and histological changes in response to obesity-promoting diets. The function and cellular location of β-catenin is finely modulated by coordinated sequences of phosphorylation-dephosphorylation events. In this article, we evaluated the levels and cellular localization of liver β-catenin variants, more specifically β-catenin phosphorylated in serine 33 (this phosphorylation provides recognizing sites for β-TrCP, which results in ubiquitination and posterior proteasomal degradation of β-catenin) and β-catenin phosphorylated in serine 675 (phosphorylation that enhances signaling and transcriptional activity of β-catenin through recruitment of different transcriptional coactivators)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28219948/genomic-integration-of-wnt-%C3%AE-catenin-and-bmp-smad1-signaling-coordinates-foregut-and-hindgut-transcriptional-program
#13
Mariana L Stevens, Praneet Chaturvedi, Scott A Rankin, Melissa Macdonald, Sajjeev Jagannathan, Masashi Yukawa, Artem Barski, Aaron M Zorn
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28219651/ho1-and-wnt-expression-is-independently-regulated-in-female-mice-brains-following-permanent-ischemic-brain-injury
#14
Jatin Tulsulkar, Alicia Ward, Zahoor Shah
A gender difference in stroke is observed throughout epidemiologic studies, pathophysiology, treatment and outcomes. We investigated the neuroprotective role of hemeoxygenase (HO) enzyme, which catabolizes free heme to bilirubin, carbon monoxide and biliverdin in the female brain after permanent ischemia. We have previously reported in male mice that genetic deletion of HO1 exacerbates the brain damage after permanent ischemia, and the mechanism of neuroprotection is dependent on the HO1/Wnt pathway; however, the role of HO1/Wnt mediated neuroprotection in the female brain is yet to be investigated...
February 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28218482/osteoblastic-differentiation-of-periodontal-ligament-stem-cells-on-non-stoichiometric-calcium-phosphate-and-titanium-surfaces
#15
L Winning, L Robinson, A R Boyd, I A El Karim, F T Lundy, B J Meenan
Bioactive materials offer particular clinical benefits in the field of dental implantology, where differentiation of stem cells towards an osteoblastic lineage is required for osseointegration and appropriate function of implants in vivo. The aim of this study was to evaluate the osteoblastic response of Stro-1+ve periodontal ligament stem cells (PDLSCs) to three well-characterised biomaterial surfaces: an abraded titanium surface (cpTi) control; a polycrystalline titanium surface, with both micro and nano-topography produced by radio frequency magnetron sputtering (TiTi); and the same surface incorporating a sputter deposited calcium phosphate coating (CaP-TiTi)...
February 20, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28217977/mir-506-enhances-the-sensitivity-of-human-colorectal-cancer-cells-to-oxaliplatin-by-suppressing-mdr1-p-gp-expression
#16
Hui Zhou, Changwei Lin, Yi Zhang, Xiuzhong Zhang, Chong Zhang, Pengbo Zhang, Xingwang Xie, Zeqiang Ren
OBJECTIVES: Chemoresistance development represents a major obstacle to the successful treatment of colorectal cancer (CRC). The aim of this study was to elucidate the mechanism by which miR-506 reverses oxaliplatin chemoresistance in CRC. METHODS: In this study, miR-506 levels were measured in 74 patients with colon cancer via quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). We subsequently analysed the relationship between miR-506 expression and CRC patient survival via the Kaplan-Meier method...
February 19, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28217374/plecanatide-mediated-activation-of-guanylate-cyclase-c-suppresses-inflammation-induced-colorectal-carcinogenesis-in-apc-min-fccc-mice
#17
Wen-Chi L Chang, Shet Masih, Anusha Thadi, Viren Patwa, Apoorva Joshi, Harry S Cooper, Vaseem A Palejwala, Margie L Clapper, Kunwar Shailubhai
AIM: To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc(+/Min-FCCC) mice with dextran sodium sulfate (DSS)-induced inflammation. METHODS: Inflammation driven colorectal carcinogenesis was induced in Apc(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide (0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid, flat and indeterminate dysplasia was evaluated...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28217097/feedback-activation-of-basic-fibroblast-growth-factor-signaling-via-the-wnt-%C3%AE-catenin-pathway-in-skin-fibroblasts
#18
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/28216017/usp7-inhibitor-p5091-inhibits-wnt-signaling-and-colorectal-tumor-growth
#19
An Tao, Gong Yaxiao, Li Xue, Kong Lingmei, Ma Pengcheng, Gong Liang, Zhu Huifang, Yu Chunlei, Liu Jianmei, Zhou Hongyu, Mao Bingyu, Li Yan
Aberrant activation of Wnt/β-catenin signaling is closely associated with the development of various human cancers, especially colorectal cancers (CRC). The ubiquitin proteasome system (UPS) is essential in the regulation of Wnt signaling and inhibitors targeting the UPS could have great potential in CRC therapy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, plays a significant role in neoplastic diseases due to its well-known function of regulating the MDM2-p53 complex. Inspired by our recent study identifying the positive role of USP7 in the Wnt signaling, we report here that USP7 is overexpressed in colorectal carcinoma cell lines and tissues, which is closely related with the poor prognosis...
February 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#20
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
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