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Wnt activators

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https://www.readbyqxmd.com/read/29779016/integrated-analysis-of-colorectal-cancer-microrna-datasets-identification-of-micrornas-associated-with-tumor-development
#1
Luca Falzone, Letizia Scola, Antonino Zanghì, Antonio Biondi, Antonio Di Cataldo, Massimo Libra, Saverio Candido
Colorectal cancer (CRC) is one of the leading cause of cancer death worldwide. Currently, no effective early diagnostic biomarkers are available for colorectal carcinoma. Therefore, there is a need to discover new molecules able to identify pre-cancerous lesions. Recently, microRNAs (miRNAs) have been associated with the onset of specific pathologies, thus the identification of miRNAs associated to colorectal cancer may be used to detect this pathology at early stages. On these bases, the expression levels of miRNAs were analyzed to compare the miRNAs expression levels of colorectal cancer samples and normal tissues in several miRNA datasets...
May 18, 2018: Aging
https://www.readbyqxmd.com/read/29778568/lnctic1-interacts-with-%C3%AE-catenin-to-drive-liver-tic-self-renewal-and-liver-tumorigenesis
#2
Zhenzhen Chen, Lintong Yao, Yating Liu, Pingping Zhu
Liver tumor-initiating cells (TICs) are drivers of liver tumorigenesis, and Wnt/β-catenin activation plays a principal role in the self-renewal of liver TICs. Despite a deep understanding of Wnt/β-catenin regulation, the roles of long noncoding RNAs (lncRNAs) in Wnt/β-catenin activation and liver TIC self-renewal are largely unknown. Here, we performed unbiased screening of lncRNAs in liver tumorigenesis and found lncTIC1 was highly expressed with liver tumorigenesis. LncTIC1 was also highly expressed in liver TICs and required for the self-renewal of liver TICs...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29778097/hyperprolactinemia-inducing-antipsychotics-increase-breast-cancer-risk-by-activating-jak-stat5-in-precancerous-lesions
#3
A N Johnston, W Bu, S Hein, S Garcia, L Camacho, L Xue, L Qin, C Nagi, S G Hilsenbeck, J Kapali, K Podsypanina, J Nangia, Y Li
BACKGROUND: Psychiatric medications are widely prescribed in the USA. Many antipsychotics cause serum hyperprolactinemia as an adverse side effect; prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling both induces cell differentiation and suppresses apoptosis. It is controversial whether these antipsychotics increase breast cancer risk. METHODS: We investigated the impact of several antipsychotics on mammary tumorigenesis initiated by retrovirus-mediated delivery of either ErbB2 or HRas or by transgenic expression of Wnt-1...
May 19, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29777010/developmental-vascular-regression-is-regulated-by-a-wnt-%C3%AE-catenin-myc-p21-cdkn1a-pathway-that-controls-cell-proliferation-and-cell-death
#4
Gowri Nayak, Yoshinobu Odaka, Vikram Prasad, Alyssa F Solano, Eun-Jin Yeo, Shruti Vemaraju, Jeffery D Molkentin, Andreas Trumpp, Bart Williams, Sujata Rao, Richard A Lang
Normal development requires tight regulation of cell proliferation and cell death. Here, we investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/β-catenin response for scheduled regression. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc , and the cyclin-dependent kinase inhibitor P21 (CDKN1A), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway coreceptors LRP5 and LRP6 have overlapping activities mediating the Wnt/β-catenin signaling in hyaloid vascular endothelial cells (VECs)...
May 18, 2018: Development
https://www.readbyqxmd.com/read/29776650/signaling-pathway-deregulation-and-molecular-alterations-across-pediatric-medulloblastomas
#5
REVIEW
B Lhermitte, A F Blandin, A Coca, E Guerin, A Durand, N Entz-Werlé
Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs)...
May 15, 2018: Neuro-Chirurgie
https://www.readbyqxmd.com/read/29776381/wnt-signaling-in-multiple-myeloma-a-central-player-in-disease-with-therapeutic-potential
#6
REVIEW
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29775181/porous-lithium-doped-hydroxyapatite-scaffold-seeded-with-hypoxia-preconditioned-bone-marrow-mesenchymal-stem-cells-for-bone-tissue-regeneration
#7
Donghai Li, Huifang Liu, Jinhai Zhao, Zhouyuan Yang, Xiaowei Xie, Zhun Wei, Dongzhe Li, Pengde Kang
Hydroxyapatite (HA) is a commonly used biomaterial in bone-tissue engineering, but pure HA is deficient in osteoinduction. In this study, we fabricated scaffolds of lithium-doped HA (Li-HA) and assess the bone generation enhancement of Li-HA scaffolds seeded with hypoxia-preconditioned bone-marrow mesenchymal stem cells (BMMSCs). We found that 1.5%Li-HA obtained optimal cell proliferation activity in vitro. In an in vivo study, Li-HA/BMSCs enhanced new bone formation, reducing the GSK-3β and increasing the β-catenin, but the angiogenic effect was not modified significantly...
May 18, 2018: Biomedical Materials
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#8
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774072/twist-promotes-tumor-metastasis-in-basal-like-breast-cancer-by-transcriptionally-upregulating-ror1
#9
Jingying Cao, Xin Wang, Tao Dai, Yuanzhong Wu, Meifang Zhang, Renxian Cao, Ruhua Zhang, Gang Wang, Rou Jiang, Binhua P Zhou, Jian Shi, Tiebang Kang
Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins...
2018: Theranostics
https://www.readbyqxmd.com/read/29773667/notch-ligand-dll1-mediates-cross-talk-between-mammary-stem-cells-and-the-macrophageal-niche
#10
Rumela Chakrabarti, Toni Celià-Terrassa, Sushil Kumar, Xiang Hang, Yong Wei, Abrar Choudhury, Julie Hwang, Jia Peng, Briana Nixon, John J Grady, Christina DeCoste, Jie Gao, Johan H van Es, Ming O Li, Iannis Aifantis, Hans Clevers, Yibin Kang
The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. Here, we show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feed back loop that promotes the function of Dll1+ MaSCs...
May 17, 2018: Science
https://www.readbyqxmd.com/read/29772510/dkk1-and-kremen-expression-predicts-the-osteoblastic-response-to-bone-metastasis
#11
Katrina L Clines, Gregory A Clines
Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis...
May 14, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29772237/lsinct5-activates-wnt-%C3%AE-catenin-signaling-by-interacting-with-ncym-to-promote-bladder-cancer-progression
#12
Xiaobo Zhu, Yuqiao Li, Shikai Zhao, Shouguo Zhao
Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are critically involved in tumor progression. In current study, we reported a novel lncRNA signature correlated with bladder cancer development. Particularly, the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is significantly upregulated in human bladder cancer cell lines and tumor specimens. Meanwhile, high LSINCT5 expression correlates with poor prognosis, enhances tumor sphere formation and invasion in vitro. In vivo xenograft tumor growth is also elevated by LSINCT5 overexpression...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29772067/dna-content-analysis-of-colorectal-serrated-lesions-detects-an-aneuploid-subset-of-inflammatory-bowel-disease-associated-serrated-epithelial-change-and-traditional-serrated-adenomas
#13
Won-Tak Choi, Kwun Wah Wen, Peter S Rabinovitch, Danning Huang, Aras N Mattis, Ryan M Gill
AIMS: Serrated lesions (SLs), including sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA), are important premalignant lesions for colorectal cancer (CRC). Although a small subset of SLs are known to harbor TP53 mutations and Wnt/β-catenin pathway activation, suggesting that they may develop dysplasia or CRC via a 'chromosomal instability (CIN)-like' pathway, it is unclear if aneuploidy (characteristic of conventional adenoma) ever develops in SLs and is associated with development of dysplasia or CRC, in this context...
May 17, 2018: Histopathology
https://www.readbyqxmd.com/read/29771996/annexin-a6-regulates-catabolic-events-in-articular-chondrocytes-via-the-modulation-of-nf-%C3%AE%C2%BAb-and-wnt-%C3%A3-catenin-signaling
#14
Takeshi Minashima, Thorsten Kirsch
Annexin A6 (AnxA6) is expressed in articular chondrocytes at levels higher than in other mesenchymal cell types. However, the role of AnxA6 in articular chondrocytes is not known. Here we show that complete lack of AnxA6 functions resulted in increased ß-catenin activation in Wnt3a-treated murine articular chondrocytes, whereas AnxA6 expressing articular chondrocytes showed decreased ß-catenin activation. High expression of AnxA6 in human articular chondrocytes showed the highest inhibition of Wnt/ß-catenin signaling...
2018: PloS One
https://www.readbyqxmd.com/read/29771446/simvastatin-induces-osteogenic-differentiation-of-mscs-via-wnt-%C3%AE-catenin-pathway-to-promote-fracture-healing
#15
M Zhang, Y-Q Bian, H-M Tao, X-F Yang, W-D Mu
OBJECTIVE: This study was designed to investigate whether Simvastatin could facilitate osteogenic differentiation of rat marrow mesenchymal stem cells (MSCs) by modulating the Wnt/β-catenin pathway, thus promoting fracture healing. MATERIALS AND METHODS: MSCs were isolated from rat bone marrow specimens and their purity was identified. The third generation of MSCs was cultured in osteoinduction medium containing simvastatin of gradient concentration, and the highest dose of simvastatin that did not cause cell proliferation was determined by the result of the CCK8 assay...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29771444/low-level-laser-irradiation-promotes-the-differentiation-of-bone-marrow-stromal-cells-into-osteoblasts-through-the-apn-wnt-%C3%AE-catenin-pathway
#16
R-F Zhang, Q Wang, A-A Zhang, J-G Xu, L-D Zhai, X-M Yang, X-T Liu
OBJECTIVE: The relationship between adiponectin (APN) pathway and Wnt pathway was explored through BMSCs, and the effect of low-level laser irradiation (LLLI) on bone marrow stromal cells (BMSCs) and its mechanism were further studied. MATERIALS AND METHODS: 3-week-old Sprague-Dawley (SD) rats were selected, and mesenchymal stem cells were separately cultured and purified. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze cell proliferation...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29771334/%C3%AE-catenin-activation-in-hair-follicle-dermal-stem-cells-induces-ectopic-hair-outgrowth-and-skin-fibrosis
#17
Yixin Tao, Qingchun Yang, Lei Wang, Jie Zhang, Xuming Zhu, Qianqian Sun, Yunbin Han, Qian Luo, Yushu Wang, Xizhi Guo, Ji Wu, Baojie Li, Xiao Yang, Lin He, Gang Ma
Hair follicle dermal sheath (DS) harbors hair follicle dermal stem cells (hfDSCs), which can be recruited to replenish DS and dermal papilla (DP). Cultured DS cells can differentiate into various cell lineages in vitro. However, it is unclear how its plasticity is modulated in vivo. Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration. Here we report that activation of β-catenin in DS generates ectopic HF outgrowth (EF) by reprogramming HF epidermal cells and DS cells themselves, and endows DS cells with hair inducing ability...
May 16, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29771197/emerging-insights-into-wnt-%C3%AE-catenin-signaling-in-head-and-neck-cancer
#18
K A Alamoud, M A Kukuruzinska
Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits...
June 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29770852/notch-inhibition-counteracts-paneth-cell-death-in-absence-of-caspase-8
#19
M K Jeon, E Kaemmerer, U Schneider, M Schiffer, C Klaus, J Hennings, T Clahsen, T Ackerstaff, M Niggemann, A Schippers, T Longerich, G Sellge, C Trautwein, N Wagner, C Liedtke, N Gassler
Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8∆int ) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity...
May 16, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29770348/quantitative-live-cell-reporter-assay-for-noncanonical-wnt-activity
#20
Edith P Karuna, Michael W Susman, Hsin-Yi Henry Ho
Noncanonical Wnt signaling functions independently of the β-catenin pathway to control diverse developmental processes, and dysfunction of the pathway contributes to a number of human pathological conditions, including birth defects and metastatic cancer. Progress in the field, however, has been hampered by the scarcity of functional assays for measuring noncanonical Wnt signaling activity. We recently described the Wnt5a-Ror-Kif26b (WRK) reporter assay, which directly monitors a post-transcriptional regulatory event in noncanonical Wnt signaling...
March 20, 2018: Bio-protocol
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