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https://www.readbyqxmd.com/read/28077837/curcumin-inhibits-gastric-carcinoma-cell-growth-and-induces-apoptosis-by-suppressing-the-wnt-%C3%AE-catenin-signaling-pathway
#1
Ruzhen Zheng, Qinghua Deng, Yuehua Liu, Pengjun Zhao
BACKGROUND Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/b-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. MATERIAL AND METHODS We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay...
January 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28069902/wnt-regulation-of-embryonic-development-likely-involves-pathways-independent-of-nuclear-ctnnb1
#2
Paula Tribulo, James I Moss, Manabu Ozawa, Zongliang Jiang, Cindy Tian, Peter J Hansen
The bovine was used to examine potential for WNT signaling to affect the preimplantation embryo. Expression of seven key genes involved in canonical WNT signaling declined to a nadir at the morula or blastocyst stage. Expression of 80 genes associated with WNT signaling in the morula and inner cell mass (ICM) and trophectoderm (TE) of the blastocyst was also evaluated. Many genes associated with WNT signaling were characterized by low transcript abundance. Seven genes were different between ICM and TE, and all of them were overexpressed in TE as compared to ICM, including WNT6, FZD1, FZD7, LRP6, PORCN, APC, and SFRP1...
January 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#3
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/28056051/mapping-the-interactome-of-a-major-mammalian-endoplasmic-reticulum-heat-shock-protein-90
#4
Feng Hong, Saleh Mohammad Rachidi, Debbie Lundgren, David Han, Xiu Huang, Hongyu Zhao, Yayoi Kimura, Hisashi Hirano, Osamu Ohara, Heichiiro Udono, Songdong Meng, Bei Liu, Zihai Li
Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins were reduced in gp96 knockdown cells, compared to levels observed in wild type cells. By immunoprecipitation, we found that 201 proteins associated with gp96...
2017: PloS One
https://www.readbyqxmd.com/read/28052259/conformational-freedom-of-the-lrp6-ectodomain-is-regulated-by-n-glycosylation-and-the-binding-of-the-wnt-antagonist-dkk1
#5
Kyoko Matoba, Emiko Mihara, Keiko Tamura-Kawakami, Naoyuki Miyazaki, Shintaro Maeda, Hidenori Hirai, Samuel Thompson, Kenji Iwasaki, Junichi Takagi
LDL-receptor-related protein 6 (LRP6) is a single-pass membrane glycoprotein with a large modular ectodomain and forms a higher order signaling platform upon binding Wnt ligands on the cell surface. Although multiple crystal structures are available for fragments of the LRP6 ectodomain, we lack a consensus view on the overall molecular architecture of the full-length LRP6 and its dynamic aspects. Here, we used negative-stain electron microscopy to probe conformational states of the entire ectodomain of LRP6 in solution and found that the four-module ectodomain undergoes a large bending motion hinged at the junction between the second and the third modules...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28042322/chromatin-remodeling-factor-lsh-is-upregulated-by-the-lrp6-gsk3%C3%AE-e2f1-axis-linking-reversely-with-survival-in-gliomas
#6
Desheng Xiao, Jun Huang, Yu Pan, Hao Li, Chunyan Fu, Chao Mao, Yan Cheng, Ying Shi, Ling Chen, Yiqun Jiang, Rui Yang, Yating Liu, Jianhua Zhou, Ya Cao, Shuang Liu, Yongguang Tao
The signaling pathway-based stratification in chromatin modification could predict clinical outcome more reliably than morphology-alone-based classification schemes in gliomas. Here we reported a role of the chromatin-remodeling factor lymphoid-specific helicase (LSH) in gliomas. Among astrocytomas of grade I to III and glioblastoma of grade IV, LSH were almost completely expressed in all cases, and strongly correlated with astrocytomas progression and poor prognosis of patients with astrocytomas and glioblastoma...
2017: Theranostics
https://www.readbyqxmd.com/read/28000854/identification-of-microrna-487b-as-a-negative-regulator-of-liver-metastasis-by-regulation-of-kras-in-colorectal-cancer
#7
Tsuyoshi Hata, Yukako Mokutani, Hidekazu Takahashi, Akira Inoue, Koji Munakata, Kazuya Nagata, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Kohei Murata, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto
Recent studies have shown that microRNAs (miRNAs) are involved in the progression of colorectal cancer (CRC). The aim of this study is to identify a novel miRNA that especially relates to liver metastasis and to explore the underlying mechanism. Differentially expressed miRNAs were analyzed using microarray, in primary CRC tumors without metastasis (n=16), those with liver metastasis (n=12), and liver metastatic lesions (n=8). We found that miR-487b level decreased in liver metastatic lesions, and qRT-PCR confirmed the results in the validating cohort (n=134)...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27919787/modulation-of-post-translational-modifications-in-%C3%AE-catenin-and-lrp6-inhibits-wnt-signaling-pathway-in-pancreatic-cancer
#8
Bharti Garg, Bhuwan Giri, Kaustav Majumder, Vikas Dudeja, Sulagna Banerjee, Ashok Saluja
β-Catenin/Wnt signaling pathway is critically regulated in a normal cell by a number of post-translational modifications. In pancreatic cancer however, aberrant activation of this pathway plays a significant role in tumor progression and metastasis. Though a number of studies have focused on understanding Wnt signaling pathway in pancreatic cancer, there has been no systematic study to evaluate molecules that may be affecting this pathway. In the current study, we used a diterpene triepoxide, triptolide, to inhibit post-translational modifications in Wnt pathway and evaluated how this compound may be affecting the intricate signaling that regulates cell proliferation in pancreatic cancer...
December 3, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27897113/strong-association-of-lipid-metabolism-related-microrna-binding-sites-polymorphisms-with-the-risk-of-late-onset-alzheimer-s-disease
#9
Lin Tan, Da-Long Zhao, Fu-Rong Sun, Meng-Shan Tan, Yu Wan, Chen-Chen Tan, Wei Zhang, Dan Miao, Jin-Tai Yu, Lan Tan
Although altered lipid metabolism has been extensively implicated in the pathogenesis of late onset Alzheimer's disease (LOAD) through cell biological and epidemiological studies, genetic studies linking lipid metabolism and LOAD are still not well understood. MicroRNAs (miRNAs) exert post-transcriptional down-regulation and their target sequence on the 3' untranslated regions (3'UTR) may be altered by single nucleotide polymorphisms (SNPs). We therefore explore whether the six loci in Clusterin gene (CLU) (rs9331949), Lipoprotein lipase gene (LPL) (rs1059507, rs3200218, rs3208305, rs3735964) and Low-density lipoprotein receptor related protein 6 (LRP6) (rs2160525) could modulate LOAD risk through the alteration of miRNA binding sites...
October 27, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27893427/cholesterol-import-and-steroidogenesis-are-biosignatures-for-gastric-cancer-patient-survival
#10
Wei-Chun Chang, Shang-Fen Huang, Yang-Ming Lee, Hsueh-Chou Lai, Bi-Hua Cheng, Wei-Chung Cheng, Jason Yen-Ping Ho, Long-Bin Jeng, Wen-Lung Ma
Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27868125/coumestrol-modulates-akt-and-wnt-%C3%AE-catenin-signaling-during-the-attenuation-of-adipogenesis
#11
Young Jin Jang, Hyo Jeong Son, Jiyun Ahn, Chang Hwa Jung, Taeyoul Ha
Coumestrol is a natural phytochemical present in plants such as red clover and soy, and has been reported to stimulate the estrogen receptor as a major phytoestrogen. While the molecular mechanisms responsible for the anti-adipogenic effects of phytoestrogens such as genistein and daidzein have been previously investigated, the effects of coumestrol on adipogenesis remain to be elucidated. We observed that coumestrol dose-dependently attenuates MDI (mixture of 3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced lipid accumulation, consistent with an earlier study, while significantly inhibiting MDI-induced adipogenesis in the first 48 hours of differentiation, a critical time window for anti-adipogenic effects...
December 7, 2016: Food & Function
https://www.readbyqxmd.com/read/27864382/molecular-dynamics-of-dkk4-modulates-wnt-action-and-regulates-meibomian-gland-development
#12
Jian Sima, Yulan Piao, Yaohui Chen, David Schlessinger
Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here, we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, which is similar to that observed in Eda-ablated Tabby mice...
December 15, 2016: Development
https://www.readbyqxmd.com/read/27854329/mir-30e-5p-and-mir-15a-synergistically-regulate-fatty-acid-metabolism-in-goat-mammary-epithelial-cells-via-lrp6-and-yap1
#13
Zhi Chen, Huiling Qiu, Liuan Ma, Jun Luo, Shuang Sun, Kang Kang, Deming Gou, Juan J Loor
MicroRNA (miRNA) regulates the expression of genes and influences a series of biological processes, including fatty acid metabolism. We screened the expression of miRNA in goat mammary glands during peak-lactation and non-lactating ("dry") periods, and performed an in vitro study with goat mammary epithelial cells (GMEC) prior to sequencing analysis. Results illustrated that miR-30e-5p and miR-15a were highly expressed. Utilizing a luciferase reporter assay and Western blot, low-density lipoprotein receptor-related protein 6 (LRP6) and Yes associated protein 1 (YAP1) genes were demonstrated to be a target of miR-30e-5p and miR-15a in GMEC...
November 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27821587/activation-proliferation-associated-protein-2-caprin-2-positively-regulates-cdk14-cyclin-y-mediated-lipoprotein-receptor-related-protein-5-and-6-lrp5-6-constitutive-phosphorylation
#14
Xin Wang, Yingying Jia, Cong Fei, Xiaomin Song, Lin Li
Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are co-receptors for Wnt ligands. Upon ligand binding, LRP5/6 undergo glycogen synthase kinase 3 (GSK3)/casein kinase I (CKI)-mediated phosphorylation at multiple PPP(S/T)P motifs in the intracellular domain, which is essential for canonical Wnt signal transduction. On the other hand, in the Wnt-off state, the mitosis-specific CDK14-Cyclin Y kinase complex phosphorylates Ser-1490 of LRP5/6 at G2/M, thereby priming the receptor for Wnt-induced phosphorylation...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27806330/plasma-glutamate-carboxypeptidase-is-a-negative-regulator-in-liver-cancer-metastasis
#15
Jae-Hye Lee, Hyun-Soo Cho, Jeong-Ju Lee, Soo Young Jun, Jun-Ho Ahn, Ju-Sik Min, Ji-Yong Yoon, Min-Hyuk Choi, Su-Jin Jeon, Jung Hwa Lim, Cho-Rok Jung, Dae-Soo Kim, Hyun-Taek Kim, Valentina M Factor, Yun-Han Lee, Snorri S Thorgeirsson, Cheol-Hee Kim, Nam-Soon Kim
Tumor metastasis is the leading cause of cancer death. In the metastatic process, EMT is a unique phenotypic change that plays an important role in cell invasion and changes in cell morphology. Despite the clinical significance, the mechanism underlying tumor metastasis is still poorly understood. Here we report a novel mechanism by which secreted plasma glutamate carboxypeptidase(PGCP) negatively involves Wnt/β-catenin signaling by DKK4 regulation in liver cancer metastasis. Pathway analysis of the RNA sequencing data showed that PGCP knockdown in liver cancer cell lines enriched the functions of cell migration, motility and mesenchymal cell differentiation...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27799526/prodigiosin-inhibits-wnt-%C3%AE-catenin-signaling-and-exerts-anticancer-activity-in-breast-cancer-cells
#16
Zhongyuan Wang, Bo Li, Liang Zhou, Shubin Yu, Zijie Su, Jiaxing Song, Qi Sun, Ou Sha, Xiaomei Wang, Wenqi Jiang, Karl Willert, Lei Wei, Dennis A Carson, Desheng Lu
Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/β-catenin pathway. Prodigiosin blocked Wnt/β-catenin signaling by targeting multiple sites of this pathway, including the low-density lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β)...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27789627/filamin-a-and-formin-2-dependent-endocytosis-regulates-proliferation-via-the-canonical-wnt-pathway
#17
Gewei Lian, Markus Dettenhofer, Jie Lu, Michael Downing, Anjen Chenn, Timothy Wong, Volney Sheen
Actin-associated proteins regulate multiple cellular processes, including proliferation and differentiation, but the molecular mechanisms underlying these processes are unclear. Here, we report that the actin-binding protein filamin A (FlnA) physically interacts with the actin-nucleating protein formin 2 (Fmn2). Loss of FlnA and Fmn2 impairs proliferation, thereby generating multiple embryonic phenotypes, including microcephaly. FlnA interacts with the Wnt co-receptor Lrp6. Loss of FlnA and Fmn2 impairs Lrp6 endocytosis, downstream Gsk3β activity, and β-catenin accumulation in the nucleus...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27780792/application-of-anti-sclerostin-therapy-in-non-osteoporosis-disease-models
#18
Christina M Jacobsen
Sclerostin, a known inhibitor of the low density lipoprotein related protein 5 and 6 (LRP5 and LRP6) cell surface signaling receptors, is integral in the maintenance of normal bone mass and strength. Patients with loss of function mutations in SOST or missense mutations in LRP5 that prevent Sclerostin from binding and inhibiting the receptor, have significantly increased bone mass. This observation leads to the development of Sclerostin neutralizing therapies to increase bone mass and strength. Anti-Sclerostin therapy has been shown to be effective at increasing bone density and strength in animal models and patients with osteoporosis...
October 22, 2016: Bone
https://www.readbyqxmd.com/read/27754059/os-15-07-role-of-pro-renin-receptor-in-the-activation-of-wnt-%C3%AE-catenin-pathway-in-colon-cancer
#19
Juan Wang, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
OBJECTIVE: Constitutive activation of Wnt/β-catenin pathway plays an important role in the pathogenesis of colon cancer; however, recent studies have also indicated that elevated Wnt levels are essential. In the present study, we investigated the potential role of (pro) renin receptor in the pathophysiology of colon cancer. DESIGN AND METHOD: (P) RR expression in human colon tissues was measured by immunohistochemistry and Western blot analysis. Human colon cancer cell lines DLD-1 with adenomatous polyposis coli (APC) truncated mutation, and HCT116 withβ-catenin activating mutation, were transfected with scramble siRNA and siRNA against (pro) renin receptor...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27751231/ubiquitin-dependent-folding-of-the-wnt-signaling-coreceptor-lrp6
#20
Elsa Perrody, Laurence Abrami, Michal Feldman, Beatrice Kunz, Sylvie Urbé, F Gisou van der Goot
Many membrane proteins fold inefficiently and require the help of enzymes and chaperones. Here we reveal a novel folding assistance system that operates on membrane proteins from the cytosolic side of the endoplasmic reticulum (ER). We show that folding of the Wnt signaling coreceptor LRP6 is promoted by ubiquitination of a specific lysine, retaining it in the ER while avoiding degradation. Subsequent ER exit requires removal of ubiquitin from this lysine by the deubiquitinating enzyme USP19. This ubiquitination-deubiquitination is conceptually reminiscent of the glucosylation-deglucosylation occurring in the ER lumen during the calnexin/calreticulin folding cycle...
October 18, 2016: ELife
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