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frizzled cancer

Min Li, Huilan Xu
OBJECTIVE: Cancer patients often experience multiple emotional distresses, particularly the fear of death. However, there are rare studies to assess the direct effect of the fear of death on disease progression. METHODS: Xenograft pancreatic cancer animal models were established in nude mice. Fear stress was induced to tumor bearing mice by closely housing with a cat and depressive behaviors were measured using open field test, forced swimming test, and sucrose consumption test...
January 11, 2019: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Abhijeet Deshmukh, Frank Arfuso, Philip Newsholme, Arun Dharmarajan
The expression and levels of secreted frizzled-related proteins (sFRPs), important Wnt signalling antagonists, have been reported to be reduced in various cancers, and are associated with disease progression and poor prognosis. During tumour development, all sFRP (1, 2, 3, 4, and 5) genes are hypermethylated, causing transcriptional silencing. sFRPs have an ability to sensitize tumour cells to chemotherapeutic drugs, enhancing cell death. Reduced Wnt signalling is associated with loss of cancer stem cell (CSC) viability...
January 30, 2019: International Journal of Biochemistry & Cell Biology
Meltem Demirel Kars, Gamze Yıldırım
Breast cancer comes second among the causes of cancer deaths of women. Although new generation hormone therapy is a promising strategy, re-occurrence or emergence of drug resistance limits the success. According to the theory of cancer stem cells (CSCs); CSCs are immortal, tumor inducing and self renewing pluripotent cells and multiply as chemotherapy proceeds, making the chemotherapy inefficient. Emerging scientific reports indicate that the mechanisms of drug resistance are the main features that CSCs gain actually...
January 29, 2019: European Journal of Pharmacology
Kaitlin J Basham, Stéphanie Rodriguez, Adina F Turcu, Antonio M Lerario, Catriona Y Logan, Madeline R Rysztak, Celso E Gomez-Sanchez, David T Breault, Bon-Kyoung Koo, Hans Clevers, Roeland Nusse, Pierre Val, Gary D Hammer
Spatiotemporal control of Wnt signaling is essential for the development and homeostasis of many tissues. The transmembrane E3 ubiquitin ligases ZNRF3 (zinc and ring finger 3) and RNF43 (ring finger protein 43) antagonize Wnt signaling by promoting degradation of frizzled receptors. ZNRF3 and RNF43 are frequently inactivated in human cancer, but the molecular and therapeutic implications remain unclear. Here, we demonstrate that adrenocortical-specific loss of ZNRF3, but not RNF43, results in adrenal hyperplasia that depends on Porcupine-mediated Wnt ligand secretion...
January 28, 2019: Genes & Development
Lei Chen, Yongqi Long, Zhijun Han, Zhizhou Yuan, Wenjin Liu, Fan Yang, Tao Li, Linfei Shu, Yunying Zhong
Dysfunction of microRNAs (miRs) has been implicated in the development and progression of various human cancers. Our previous study demonstrated that miR-101 inhibited bladder cancer cell proliferation and invasion through inhibition of c-FOS expression. As an miR generally has many targets, other targets of miR-101 may also serve important roles in bladder cancer progression. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to examine mRNA and protein expression, respectively...
February 2019: Experimental and Therapeutic Medicine
Cheng-Wei Chu, Huey-Jiun Ko, Chia-Hua Chou, Tai-Shan Cheng, Hui-Wen Cheng, Yu-Hsin Liang, Yun-Ling Lai, Chen-Yen Lin, Chihuei Wang, Joon-Khim Loh, Jiin-Tsuey Cheng, Shean-Jaw Chiou, Chun-Li Su, Chi-Ying F Huang, Yi-Ren Hong
Thioridazine (THD) is a common phenothiazine antipsychotic drug reported to suppress growth in several types of cancer cells. We previously showed that THD acts as an antiglioblastoma and anticancer stem-like cell agent. However, the signaling pathway underlying autophagy and apoptosis induction remains unclear. THD treatment significantly induced autophagy with upregulated AMPK activity and engendered cell death with increased sub-G1 in glioblastoma multiform (GBM) cell lines. Notably, through whole gene expression screening with THD treatment, frizzled (Fzd) proteins, a family of G-protein-coupled receptors, were found, suggesting the participation of Wnt/β-catenin signaling...
January 22, 2019: International Journal of Molecular Sciences
Huohui Ou, Zhanjun Chen, Leyang Xiang, Yinghao Fang, Yuyan Xu, Qin Liu, Zhigang Hu, Xianghong Li, Yu Huang, Dinghua Yang
Prior observation has indicated that Frizzled 2 (FZD2)-induced epithelial-mesenchymal transition (EMT) may be a key step in metastasis and early recurrence of hepatocellular carcinoma (HCC). However, the mechanism underlying tumor development and progression due to aberrant FZD2 expression is poorly defined. Here, we provide evidence that FZD2 is a driver for EMT, cancer stem cell (CSC) property, and vasculogenic mimicry (VM) in HCC. We found that FZD2 was highly expressed in two cohorts of Chinese hepatitis B virus-related HCC patients, and that high FZD2 expression was associated with poor prognosis...
January 24, 2019: Cancer Science
Julie E McGrath, Louis Panzica, Ryan Ransom, Henry G Withers, Irwin H Gelman
Cancer tumor cell dormancy is a significant clinical problem in breast cancer (BrCa). We used a 3D in vitro model of the endosteal bone niche (EN), consisting of endothelial, bone marrow stromal cells and fetal osteoblasts in a 3D collagen matrix (GELFOAMTM), to identify genes required for dormancy. Human triple-negative MDA-MB-231 BrCa cells, but not the bone-tropic metastatic variant, BoM1833, established dormancy in 3D-EN cultures in a p38-MAPK-dependent manner, whereas both cell types proliferated on 2D plastic or in 3D collagen alone...
January 16, 2019: Molecular Cancer Research: MCR
Jiangbo Wang, Xiu-Rong Ren, Hailan Piao, Shengli Zhao, Takuya Osada, Richard T Premont, Robert A Mook, Michael A Morse, Herbert Kim Lyerly, Wei Chen
The Wnt signaling pathway, known for regulating genes critical to normal embryonic development and tissue homeostasis, is dysregulated in many types of cancer. Previously we identified that the anthelmintic drug niclosamide inhibited  Wnt signaling by promoting internalization of Wnt receptor Frizzled 1 and degradation of  Wnt signaling pathway proteins Dishevelled 2 and β-catenin, contributing to suppression of colorectal cancer growth in vitro and in vivo   Here we provide evidence that niclosamide-mediated inhibition of Wnt signaling is mediated through autophagosomes induced by niclosamide...
January 11, 2019: Biochemical Journal
Dustin Flanagan, Nick Barker, Natasha S Di Costanzo, Elizabeth Anne Mason, Austin Gurney, Valerie S Meniel, Sarah Koushyar, Chloe R Austin, Helen B Pearson, Alex Boussioutas, Hans Clevers, Toby J Phesse, Elisabeth Vincan
A subset of gastric cancer (GC) patients have mutations in genes that participate in or regulate Wnt signaling at the level of ligand (Wnt) receptor (Fzd) binding. Moreover, increased Fzd expression is associated with poor clinical outcome. Despite these findings, there are no in vivo studies investigating the potential of targeting Wnt receptors for treating GC, and the specific Wnt receptor transmitting oncogenic Wnt signaling in GC is unknown. Here we use inhibitors of Wnt/Fzd (OMP-18R5/Vantictumab) and conditional gene deletion to test the therapeutic potential of targeting Wnt signaling in preclinical models of intestinal-type gastric cancer and ex vivo organoid cultures...
January 8, 2019: Cancer Research
Amit Tirosh, Sanjit Mukherjee, Justin Lack, Sudheer Kumar Gara, Sophie Wang, Martha M Quezado, Xavier M Keutgen, Xiaolin Wu, Maggie Cam, Suresh Kumar, Dhaval Patel, Naris Nilubol, Monica Varun Tyagi, Electron Kebebew
BACKGROUND: Aberrant methylation is a known cause of cancer initiation and/or progression. There are scant data on the genome-wide methylation pattern of nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) and sporadic and hereditary NFPanNETs. METHODS: Thirty-three tissue samples were analyzed: they included samples from sporadic (n = 9), von Hippel-Lindau (VHL)-related (n = 10), and multiple endocrine neoplasia type 1 (MEN1)-related NFPanNETs (n = 10) as well as normal islet cells (n = 4) for comparison...
January 8, 2019: Cancer
Holly V Shaw, Alexey Koval, Vladimir L Katanaev
Frizzleds (FZDs) are a family of GPCRs controlling key events in all branches of the developmental Wnt signaling pathway. In this capacity these receptors are mostly active prenatally and have only a limited set of functions in the human adult. Numerous cancer types and subtypes were shown to be dependent on aberrant Wnt signaling and FZDs in particular. Taken together with their GPCR properties, this makes them an attractive drug target for the development of highly specific and efficient targeted therapies against cancer...
2019: Methods in Cell Biology
Ismael Reyes, Niradiz Reyes, Robert Suriano, Codrin Iacob, Nina Suslina, Anthony Policastro, Augustine Moscatello, Stimson Schantz, Raj K Tiwari, Jan Geliebter
BACKGROUND: Thyroid cancer is the most common endocrine malignancy worldwide, with the predominant form papillary thyroid carcinoma (PTC) representing approximately 80% of cases. OBJECTIVE: This study was addressed to identify potential genes and pathways involved in the pathogenesis of PTC and potential novel biomarkers for this disease. METHODS: Gene expression profiling was carried out by DNA microarray technology. Validation of microarray data by qRT-PCR, western blot, and enzyme linked immunosorbent assay was also performed in a selected set of genes and gene products, with the potential to be used as diagnostic or prognostic biomarkers, such as those associated with cell adhesion, extracellular matrix (ECM) remodeling and immune/inflammatory response...
December 22, 2018: Cancer Biomarkers: Section A of Disease Markers
Lucia Poggi, Simona Casarosa, Matthias Carl
The coordinated interplay between extrinsic activating and repressing cell signaling molecules is pivotal for embryonic development and subsequent tissue homeostasis. This is well exemplified by studies on the evolutionarily conserved Wnt signaling pathways. Tight temporal and spatial regulation of Wnt signaling activity is required throughout lifetime, from maternal stages before gastrulation until and throughout adulthood. Outside cells, the action of numerous Wnt ligands is counteracted and fine-tuned by only a handful of well characterized secreted inhibitors, such as for instance Dickkopf, secreted Frizzled Related Proteins and Cerberus...
2018: Frontiers in Cell and Developmental Biology
Robert A Mook, Jiangbo Wang, Xiu-Rong Ren, Hailan Piao, H Kim Lyerly, Wei Chen
Dysregulation of the Wnt signaling pathway is an underlying mechanism in multiple diseases, particularly in cancer. Until recently, identifying agents that target this pathway has been difficult and as a result, no approved drugs exist that specifically target this pathway. We reported previously that the anthelmintic drug Niclosamide inhibits the Wnt/β-catenin signaling pathway and suppresses colorectal cancer cell growth in vitro and in vivo. In an effort to build on this finding, we sought to discover new Wnt/β-catenin inhibitors that expanded the chemotype structural diversity...
November 12, 2018: Bioorganic & Medicinal Chemistry Letters
Ming Tan, Mohammad Asad, Valerie Heong, Meng Kang Wong, Tuan Zea Tan, Jieru Ye, Kuee Theng Kuay, Jean Paul Thiery, Clare Scott, Ruby Yun-Ju Huang
Frizzled family receptor 7 (FZD7), a Wnt signaling receptor, is associated with the maintenance of stem cell properties and cancer progression. FZD7 has emerged as a potential therapeutic target because it is capable of transducing both canonical and non-canonical Wnt signals. In this study, we investigated the regulatory pathway downstream of FZD7 and its functional roles. We found that FZD7 expression was crucial to the maintenance of the mesenchymal phenotype, anoikis resistance, and spheroid and tumour formation in ovarian cancer...
December 11, 2018: Molecular Oncology
Ji-Xiang Peng, Shun-Yu Liang, Li Li
Secreted frizzled‑related protein 1 (sFRP1) is an inhibitor of canonical Wnt signaling; however, previous studies have determined a tumor‑promoting function of sFRP1 in a number of different cancer types. A previous study demonstrated that sFRP1 overexpression was associated with an aggressive phenotype and the activation of transforming growth factor β (TGFβ) signaling. sFRP1 overexpression and sFRP1 knockdown cell models were established. Immunoblotting was conducted to examine the protein levels of the associated molecules...
October 31, 2018: Oncology Reports
William J J Finlay, James E Coleman, Jonathan S Edwards, Kevin S Johnson
Monoclonal anti-programmed cell death 1 (PD1) antibodies are successful cancer therapeutics, but it is not well understood why individual antibodies should have idiosyncratic side-effects. As the humanized antibody SHR-1210 causes capillary hemangioma in patients, a unique toxicity amongst anti-PD1 antibodies, we performed human receptor proteome screening to identify nonspecific interactions that might drive angiogenesis. This screen identified that SHR-1210 mediated aberrant, but highly selective, low affinity binding to human receptors such as vascular endothelial growth factor receptor 2 (VEGFR2), frizzled class receptor 5 and UL16 binding protein 2 (ULBP2)...
December 12, 2018: MAbs
Aaron H Nile, Rami N Hannoush
Wnt signaling regulates physiological processes ranging from cell differentiation to bone formation. Dysregulation of Wnt signaling is linked to several human ailments, including colorectal, pancreatic, and breast cancers. As such, modulation of this pathway has been an attractive strategy for therapeutic development of anticancer agents. Since the discovery of Wnt proteins more than 35 years ago, research efforts continue to focus on understanding the biochemistry of their molecular interactions and their biological functions...
December 10, 2018: Journal of Biological Chemistry
Kexu Chen, Hanlin Liang, Jiewen Peng, Yanfang Zheng
OBJECTIVE: To investigate the expressions of secreted frizzled-related protein 4 (SFRP4) in stage Ⅱ DNA mismatch repair-deficient (dMMR) and mismatch repair- proficient (pMMR) colorectal cancers and explore their clinical significance. METHODS: We collected fresh stage Ⅱ colon cancer tissues with different MMR status detected by immunohistochemistry (IHC). The differentially expressed mRNAs between dMMR and pMMR tumors were identified by Affymetrix Human oeLncRNA gene chip, and the expression of SFRP4 in these cancer tissues and in colorectal cancer cell lines were detected using Western blotting and real- time quantitative PCR...
November 30, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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