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Fzd10 wnt pathway

Yisong Xu, Cheng Zhang, Hui Liang, Shanshuang Hu, Pengkun Li, Linna Liu, Xianglong Duan, Chao Chen, Yani Zhang, Penggao Dai
Acquired resistance to 5-fluorouracil (5-FU) frequently occurs in patients with hepatocellular carcinoma (HCC), the underlying molecular mechanisms of which are poorly understood. The aim of this study was to identify candidate genes and associated signalling pathways that may play a role in developing drug resistance following repeated 5-FU treatments. In this work, we established 5-FU-resistant cells (HepG2/5-FU) using stepwise increasing concentrations of 5-FU in parental HepG2 cells. Using transcriptome sequencing, we found that the expressions of the Wnt signalling genes, including negative regulators (DKK1, DKK3, ZNRF3, RNF43 and APC2) and positive regulators (FZD10 and DVL1), were significantly downregulated and upregulated in HepG2/5-FU cells, respectively, resulting in increased Wnt signalling...
March 27, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Zhenzhen Chen, Yanfeng Gao, Lintong Yao, Yating Liu, Lan Huang, Zhongyi Yan, Wenshan Zhao, Pingping Zhu, Haibo Weng
Liver tumor-initiating cells (TICs), the drivers for liver tumorigenesis, accounts for liver tumor initiation, metastasis, drug resistance and relapse. Wnt/β-catenin signaling pathway emerges as a critical modulator in liver TIC self-renewal. However, the molecular mechanism of Wnt/β-catenin initiation in liver tumorigenesis and liver TICs is still elusive. Here, we examined the expression pattern of 10 Wnt receptors (FZD1-FZD10), and found only FZD6 is overexpressed along with liver tumorigenesis. What's more, a divergent lncRNA of FZD6, termed lncFZD6, is also highly expressed in liver cancer and liver TICs...
March 14, 2018: Oncogene
Yicheng Chen, Qiaoli Huang, Hua Zhou, Yueping Wang, Xian Hu, Tao Li
Leflunomide (LEF), an inhibitor of dihydroorotate dehydrogenase (DHODH) in pyrimidine biosynthetic pathway, is an immunomodulatory agent approved for the treatment of rheumatoid arthritis. In this study, we show that LEF significantly reduced cell proliferation of renal carcinoma cells in a concentration-dependent manner. LEF at 50 μM induced S-phase arrest and autophagy. Higher doses of LEF (>50 μM) effectively induced cell apoptosis. Modulating the concentration of LEF resulted in distinct effects on the expression of regulatory proteins associated with cell cycle, apoptosis, and autophagy...
August 2, 2016: Oncotarget
Paul W Hamilton, Yu Sun, Jonathan J Henry
The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens...
April 2016: Experimental Eye Research
Qian Sun, Ronghua Wang, Jing Luo, Peng Wang, Si Xiong, Man Liu, Bin Cheng
Hepatitis B virus X protein (HBx) is implicated in the pathogenesis of hepatocellular carcinoma (HCC) via a network of signaling pathways. Notch pathway is a major member of the network. Notch signaling may generate opposing effect in different steps of carcinogenesis, depending on the tumor cell type and the status of other signaling pathways, such as Wnt signaling pathway. Our previous studies have shown that activated Notch1 signaling is required for HBx to promote proliferation and survival of human hepatic cell line L02...
October 2014: International Journal of Oncology
Lisa M Galli, Linda A Szabo, Lydia Li, Yin Min Htaik, Ouma Onguka, Laura W Burrus
BACKGROUND: WNTLESS (WLS) is a multi-transmembrane protein that transports Wnt ligands from the Golgi to the cell surface. Although WLS loss-of-function experiments in the developing central nervous system reveal phenotypes consistent with defects in WNT1 and WNT3A signaling, data from complementary gain-of-function experiments have not yet been reported. Here, we report the phenotypic consequences of WLS overexpression in cultured cells and in the developing chick spinal cord. RESULTS: Overexpression of small amounts of WLS along with either WNT1 or WNT3A promotes the Wnt/β-catenin pathway in HEK293T cells, while overexpression of higher levels of WLS inhibits the Wnt/β-catenin pathway in these cells...
September 2014: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Sérgia Velho, Ana Pinto, Danilo Licastro, Maria José Oliveira, Filipa Sousa, Elia Stupka, Raquel Seruca
BACKGROUND: MLK3 gene mutations were described to occur in about 20% of microsatellite unstable gastrointestinal cancers and to harbor oncogenic activity. In particular, mutation P252H, located in the kinase domain, was found to have a strong transforming potential, and to promote the growth of highly invasive tumors when subcutaneously injected in nude mice. Nevertheless, the molecular mechanism underlying the oncogenic activity of P252H mutant remained elusive. METHODS: In this work, we performed Illumina Whole Genome arrays on three biological replicas of human HEK293 cells stably transfected with the wild-type MLK3, the P252H mutation and with the empty vector (Mock) in order to identify the putative signaling pathways associated with P252H mutation...
2014: BMC Cancer
Carmen García-Ibarbia, Jesús Delgado-Calle, Iñigo Casafont, Javier Velasco, Jana Arozamena, María I Pérez-Núñez, María A Alonso, María T Berciano, Fernando Ortiz, José L Pérez-Castrillón, Agustín F Fernández, Mario F Fraga, María T Zarrabeitia, José A Riancho
We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic and epigenetic mechanisms involved. β-Catenin gene expression and nuclear levels were analyzed by real time PCR and confocal immunofluorescence. Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 units vs. 76 ± 12, p=0.01, n=10), without differences in gene transcription, which is consistent with a post-translational down-regulation of β-catenin and decreased Wnt pathway activity...
December 15, 2013: Gene
Masataka Nikaido, Edward W P Law, Robert N Kelsh
Wnt signaling is crucial for the regulation of numerous processes in development. Consistent with this, the gene families for both the ligands (Wnts) and receptors (Frizzleds) are very large. Surprisingly, while we have a reasonable understanding of the Wnt ligands likely to mediate specific Wnt-dependent processes, the corresponding receptors usually remain to be elucidated. Taking advantage of the zebrafish model's excellent genomic and genetic properties, we undertook a comprehensive analysis of the expression patterns of frizzled (fzd) genes in zebrafish...
2013: PloS One
Hui Cai, Mark A Fields, Risa Hoshino, Lucian V Del Priore
OBJECTIVE: To determine the effects of age and topographic location on gene expression in human neural retina. METHODS: Macular and peripheral neural retina RNA was isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses. RESULTS: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula, and peripheral retina cluster into four distinct groups...
2012: Frontiers in Aging Neuroscience
Ettore Salsano, Rosina Paterra, Miriam Figus, Francesca Menghi, Emanuela Maderna, Bianca Pollo, Carlo Lazzaro Solero, Luca Massimi, Gaetano Finocchiaro
Secreted WNT proteins signal through ten receptors of the frizzled (FZD) family. Because of the relevance of the WNT/β-catenin (CTNNB1) signaling pathway in medulloblastomas (MBs), we investigated the expression of all ten members of the FZD gene family (FZD1-10) in 17 human MBs, four MB cell lines and in normal human cerebellum, using real-time PCR. We found that FZD2 transcript was over-expressed in all MBs and MB cell lines. Western blot analysis confirmed the expression of FZD2 at the protein level. Moreover, the levels of FZD2 transcript were found to correlate with those of ASPM transcript, a marker of mitosis essential for mitotic spindle function...
January 2012: Journal of Neuro-oncology
Hye Won Shin, Soo Young Park, Kyoung Bun Lee, Eun Shin, Suk Woo Nam, Jung Young Lee, Ja June Jang
BACKGROUND/AIMS: This study aimed to better understand gene expression profiles of human hepatic stellate cell (HSC) activation and the relationship with the Wnt signaling pathway. METHODS: The global transcript levels in platelet derived growth factor-BB (PDGF-BB)-stimulated hTERT HSCs were analyzed using oligonucleotide microarrays. Oligonucleotide microarrays with 19K human oligo chips were performed to obtain gene expression profiles associated with proliferation in human hTERT HSCs...
December 2009: Korean Journal of Hepatology
Grace E Snow, Allison C Kasper, Alexander M Busch, Elisabeth Schwarz, Katherine E Ewings, Thomas Bee, Michael J Spinella, Ethan Dmitrovsky, Sarah J Freemantle
BACKGROUND: Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency...
October 29, 2009: BMC Cancer
Poongodi Geetha-Loganathan, Suresh Nimmagadda, Laurent Antoni, Katherine Fu, Cheryl J Whiting, Philippa Francis-West, Joy M Richman
A comprehensive expression analysis of WNT signalling pathway genes during several stages of chicken facial development was performed. Thirty genes were surveyed including: WNT1, 2B, 3A, 4, 5A, 5B, 6, 7A, 7B, 8B, 8C, 9A, 9B, 11, 11B, 16, CTNNB1, LEF1, FRZB1, DKK1, DKK2, FZD1-8, FZD10. The strictly canonical WNTs (2B, 7A, 9B, and 16) in addition to WNT4 WNT6 (both canonical and non-canonical) are epithelially expressed, whereas WNT5A, 5B, 11 are limited to the mesenchyme. WNT16 is limited to the invaginating nasal pit, respiratory epithelium, and lip fusion zone...
May 2009: Developmental Dynamics: An Official Publication of the American Association of Anatomists
C Fukukawa, S Nagayama, T Tsunoda, J Toguchida, Y Nakamura, T Katagiri
We previously reported that Frizzled homologue 10 (FZD10), a member of the Wnt signal receptor family, was highly and specifically upregulated in synovial sarcoma and played critical roles in its cell survival and growth. We here report a possible molecular mechanism of the FZD10 signaling in synovial sarcoma cells. We found a significant enhancement of phosphorylation of the Dishevelled (Dvl)2/Dvl3 complex as well as activation of the Rac1-JNK cascade in synovial sarcoma cells in which FZD10 was overexpressed...
February 26, 2009: Oncogene
Satoshi Nagayama, Eiji Yamada, Yoshiki Kohno, Tomoki Aoyama, Chikako Fukukawa, Hajime Kubo, Go Watanabe, Toyomasa Katagiri, Yusuke Nakamura, Yoshiharu Sakai, Junya Toguchida
We investigated the immunohistochemical expression patterns of Frizzled homolog 10 (FZD10), a cell-surface receptor for molecules in the Wnt pathway, in tissue samples derived from 104 patients with colorectal cancers (CRCs). There was no immunoreactivity for FZD10 in normal colonic mucosa, and only tumor cells in polyps and CRC tissues showed spotted immunostaining patterns in apical sides of the cytoplasm. In metastatic liver lesions, tumor cells showed cytoplasmic immunostaining similar to primary lesions, whereas normal liver parenchyma showed almost no immunostaining...
March 2009: Cancer Science
Dingzhi Huang, Quanli Gao, Liping Guo, Chunpeng Zhang, Wei Jiang, Hongxia Li, Jing Wang, Xiaohong Han, Yuankai Shi, Shih Hsin Lu
Side population (SP) cells may play an important role in tumorigenesis and cancer therapy. We isolate and identify the cancer stem-like cells in human esophageal carcinoma (EC) cell lines, EC9706 and EC109 cells labeled with Hoechst 33342. Both the cell lines contained SP cells, and the cells that had the strongest dye efflux activity ("Tip"-SP cell) in EC9706 had higher clone formation efficiency than non-SP cells. When transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, "Tip"-SP cells showed at least 50 times higher tumorigenicity than non-SP cells...
April 2009: Stem Cells and Development
Masaru Katoh
WNT family members are secreted-type glycoproteins to orchestrate embryogenesis, to maintain homeostasis, and to induce pathological conditions. FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, FZD10, LRP5, LRP6, and ROR2 are transmembrane receptors transducing WNT signals based on ligand-dependent preferentiality for caveolin- or clathrin-mediated endocytosis. WNT signals are transduced to canonical pathway for cell fate determination, and to non-canonical pathways for regulation of planar cell polarity, cell adhesion, and motility...
July 2008: Current Drug Targets
Kendra S Carmon, David S Loose
In the endometrium, hormonal effects on epithelial cells are often elicited through stromal hormone receptors via unknown paracrine mechanisms. Several lines of evidence support the hypothesis that Wnts participate in stromal-epithelial cell communication. Wnt7a is expressed in the luminal epithelium, whereas the extracellular modulator of Wnt signaling, secreted frizzled-related protein 4 (SFRP4), is localized to the stroma. Studies have reported that SFRP4 expression is significantly decreased in endometrial carcinoma and that both SFRP4 and Wnt7a genes are differentially regulated in response to estrogenic stimuli...
June 2008: Molecular Cancer Research: MCR
Masaru Katoh
The biological functions of some orthologs within the human genome and model-animal genomes are evolutionarily conserved, but those of others are divergent due to protein evolution and promoter evolution. Because WNT signaling molecules play key roles during embryogenesis, tissue regeneration and carcinogenesis, the author's group has carried out a human WNT-ome project for the comprehensive characterization of human genes encoding WNT signaling molecules. From 1996 to 2002, we cloned and characterized WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT9A/WNT14, WNT9B/WNT14B, WNT10A, WNT10B, WNT11, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD10, FRAT1, FRAT2, NKD1, NKD2, VANGL1, RHOU/ARHU, RHOV/ARHV, GIPC2, GIPC3, FBXW11/betaTRCP2, SOX17, TCF7L1/TCF3, and established a cDNA-PCR system for snap-shot and dynamic analyses on the WNT-transcriptome...
January 2007: Stem Cell Reviews
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