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https://www.readbyqxmd.com/read/30333256/lncrna-awpph-promotes-the-growth-of-triple-negative-breast-cancer-by-up-regulating-frizzled-homolog-7-fzd7
#1
Kainan Wang, Xuelu Li, Chen Song, Man Li
BACKGROUND: LncRNA AWPPH is a recently identified critical player in development of several types of human malignancies, our study aimed to investigate the role of AWPPH in triple-negative breast cancer. METHODS: In this study, expression of AWPPH in tumor tissues and adjacent healthy tissues of patients with triple-negative breast cancer as well as in plasma of both patients and healthy people was detected by qRT-PCR. Application potentials of AWPPH in the diagnosis and prognosis of triple-negative breast cancer were evaluated by ROC curve analysis and survival curve analysis, respectively...
October 17, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/30309741/structural-and-druggability-landscape-of-frizzled-g-protein-coupled-receptors
#2
REVIEW
Xianjun Zhang, Shaowei Dong, Fei Xu
Class Frizzled G protein-coupled receptors (GPCRs), which includes the Smoothened receptor (SMO) and 10 Frizzled receptors (FZDs), are responsible for mediating fundamental signaling in embryonic development and tissue homeostasis. Dysregulation of these receptors can lead to cancer. Structural understanding of these molecules has provided insight to their function and signaling, and guided drug discovery. To date, the structures of the multi- and individual domains of SMO, 14 FZD extracellular domains, and the transmembrane domain (TMD) of FZD4, have been reported...
October 8, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/30260048/individual-or-combination-treatments-with-lapatinib-and-paclitaxel-cause-potential-bone-loss-and-bone-marrow-adiposity-in-rats
#3
Alice M C Lee, Joanne M Bowen, Yu-Wen Su, Erin Plews, Rosa Chung, Dorothy M K Keefe, Cory J Xian
Cancer treatments with cytotoxic drugs have been shown to cause bone loss. However, effects on bone are less clear for ErbB-targeting tyrosine kinase inhibitors or their combination use with cytotoxic drugs. This study examined the effects of individual or combination treatments with breast cancer drugs lapatinib (a dual ErbB1/ErbB2 inhibitor) and paclitaxel (a microtubule-stabilizing cytotoxic agent) on bone and bone marrow of rats. Wistar rats received lapatinib (240 mg/kg) daily, paclitaxel (12 mg/kg) weekly, or their combination for 4 weeks, and effects on bone/bone marrow were examined at the end of week 4...
September 27, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30255827/adherence-to-the-world-cancer-research-fund-american-institute-for-cancer-research-cancer-prevention-recommendations-and-wnt-pathway-related-markers-of-bowel-cancer-risk
#4
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Seamus Kelly, David Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies...
September 26, 2018: British Journal of Nutrition
https://www.readbyqxmd.com/read/30235453/mir-191-inhibition-induces-apoptosis-through-reactivating-secreted-frizzled-related-protein-1-in-cholangiocarcinoma
#5
Peng-Cheng Kang, Kai-Ming Leng, Yue-Ping Liu, Yang Liu, Yi Xu, Wei Qin, Jian-Jun Gao, Zhi-Dong Wang, Sheng Tai, Xiang-Yu Zhong, Yun-Fu Cui
BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30191337/structural-and-dynamic-characterization-of-human-wnt2-fzd7-complex-using-computational-approaches
#6
Hourieh Kalhor, Mansour Poorebrahim, Hamzeh Rahimi, Ali Akbar Shabani, Morteza Karimipoor, Mohammad Reza Akbari Eidgahi, Ladan Teimoori-Toolabi
Wnt and Frizzled (Fzd) family members play crucial roles in the self-renewal of tumor-initiating cells. Until now, only a few studies have addressed the distinct mechanism of Wnt-Fzd interactions. In this study, we suggest a possible interaction mode of Wnt2 with the Fzd7 cysteine-rich domain (CRD)-both of which are up-regulated in some types of cancer. A combination of homology modeling, molecular docking and molecular dynamics (MD) simulations was carried out to study this ligand-receptor complex in great detail...
September 6, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/30183492/a-synthetic-anti-frizzled-antibody-engineered-for-broadened-specificity-exhibits-enhanced-anti-tumor-properties
#7
Zvezdan Pavlovic, Jarrett J Adams, Levi L Blazer, Amandeep K Gakhal, Nick Jarvik, Zachary Steinhart, Mélanie Robitaille, Keith Mascall, James Pan, Stephane Angers, Jason Moffat, Sachdev S Sidhu
Secreted Wnt ligands play a major role in the development and progression of many cancers by modulating signaling through cell-surface Frizzled receptors (FZDs). In order to achieve maximal effect on Wnt signaling by targeting the cell surface, we developed a synthetic antibody targeting six of the 10 human FZDs. We first identified an anti-FZD antagonist antibody (F2) with a specificity profile matching that of OMP-18R5, a monoclonal antibody that inhibits growth of many cancers by targeting FZD7, FZD1, FZD2, FZD5 and FZD8...
September 25, 2018: MAbs
https://www.readbyqxmd.com/read/30158579/rab37-mediates-exocytosis-of-secreted-frizzled-related-protein-1-to-inhibit-wnt-signaling-and-thus-suppress-lung-cancer-stemness
#8
Shu-Huei Cho, I-Ying Kuo, Pei-Jung Frank Lu, Hong-Tai Tzeng, Wu-Wei Lai, Wu-Chou Su, Yi-Ching Wang
Recent studies have revealed that dysregulated Rab small GTPase-mediated vesicle trafficking pathways are associated with cancer progression. However, whether any of the Rabs plays a suppressor role in cancer stemness is least explored. Rab37 has been postulated as a tumor suppressive small GTPase for trafficking anti-tumor cargos. Here, we report a previously uncharacterized mechanism by which Rab37 mediates exocytosis of secreted frizzled-related protein-1 (SFRP1), an extracellular antagonist of Wnt, to suppress Wnt signaling and cancer stemness in vitro and in vivo...
August 29, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/30142536/microrna-504-functions-as-a-tumor-suppressor-in-hepatocellular-carcinoma-through-inhibiting-frizzled-7-mediated-wnt-%C3%AE-catenin-signaling
#9
Hui Quan, Bo Li, Jianjun Yang
Accumulating evidence suggests that microRNAs (miRNAs) are critical regulators in the development and progression of various malignant tumors, including hepatocellular carcinoma (HCC). Multiple findings have indicated that miRNA-504 (miR-504) is dysregulated in several types of cancers, functioning as an oncogenic miRNA or a tumor suppressive miRNA. However, the role of miR-504 in HCC remains unknown. In this study, we aimed to detect the expression pattern of miR-504 in HCC tissues and cell lines and investigate the precise biological function in HCC cells...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30137666/wnt-signaling-in-human-and-mouse-breast-cancer-focusing-on-wnt-ligands-receptors-and-antagonists
#10
Ping Yin, Wei Wang, Zhongbo Zhang, Yu Bai, Jian Gao, Chenghai Zhao
Wnt proteins, a group of secreted glycoproteins, mainly combine with receptors Frizzled (FZD) and/or LDL receptor-related proteins 5/6 (LRP5/6), initiating β-catenin-dependent and -independent signaling pathways. These pathways, which can be regulated by some secreted antagonists such as secreted Frizzled-related proteins (SRFP) and DKK, play a critical role in embryo development and adult homeostasis. Overactivation of Wnt signaling has been implicated in some human diseases including cancer. Wnt transgenic mice provide convincing evidence that Wnt signaling is involved in breast cancer initiation and progression, which is further strengthened by observations on clinical human breast cancer patients and studies on in vitro cultured human breast cancer cells...
August 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/30097126/wnt-%C3%AE-catenin-signaling-pathway-is-involved-in-regulating-the-migration-by-an-effective-natural-compound-brucine-in-lovo-cells
#11
Xianpeng Shi, Man Zhu, Yuan Kang, Tianfeng Yang, Xia Chen, Yanmin Zhang
BACKGROUND: Colorectal cancer remains the third most common malignancies and migration is one of the main factors for its high mortality rate. Brucine, a natural plant alkaloid, has been proved to possess a variety of pharmacological functions including anti-tumor activities. PURPOSE: The aim of this study was to investigate the inhibitory effect of brucine on the colorectal cancer and the underlying mechanism. METHODS: In this study, colony formation assay and transwell assay were used to investigate the effect of brucine on LoVo cells viability and migration...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/30096373/a-novel-recombinant-human-frizzled-7-protein-exhibits-anti-tumor-activity-against-triple-negative-breast-cancer-via-abating-wnt-%C3%AE-catenin-pathway
#12
Wei Xie, Yan Zhang, Yuan He, Kunchi Zhang, Guoqing Wan, Yanjuan Huang, Zhaoli Zhou, Gang Huang, Jin Wang
Triple negative breast cancer (TNBC) is one of the most difficult malignancy to treat due to a lack of targeted therapy. Studies have demonstrated that the activation of Wnt/β-catenin signaling was preferentially found in TNBC. Frizzled-7 (Fzd7), one of the Wnt receptors, was significantly up-regulated in TNBC and modulated TNBC tumorigenesis through the Wnt signaling pathway, indicating Fzd7 is a biomarker and a potential therapeutic target for TNBC. Here, we designed a recombinant soluble peptide fragment (rhFzd7) to antagonize Fzd7 by competitively binding with Wnt ligands...
August 7, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/30094104/chemoresistance-and-targeting-of-growth-factors-cytokines-signalling-pathways-towards-the-development-of-effective-therapeutic-strategy-for-endometrial-cancer
#13
REVIEW
Fengjun Guo, Haina Zhang, Zanhui Jia, Manhua Cui, Jingyan Tian
Endometrial cancer tends to be an aggressive malignancy. Although the disease prognosis can be good at the early stages of disease, the advanced condition is not curable. Chemotherapy regimens and hormone-based therapy in combination with surgery are major approaches for the management of endometrial cancers. However, intrinsic chemoresistance reduces the success rate and increases the possibility of disease relapse. Investigation of underlying mechanisms revealed altered activation of PI3K/AKT, MAPK, fibroblast growth factor (FGF), mTOR and WNT pathways and reduced gene expression of tumor suppressor p53 in recurrent endometrial cancer...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/30076960/a-novel-porcupine-inhibitor-blocks-wnt-pathways-and-attenuates-cardiac-hypertrophy
#14
Jiahui Jiang, Cong Lan, Liangpeng Li, Dezhong Yang, Xuewei Xia, Qiao Liao, Wenbin Fu, Xiongwen Chen, Songzhu An, Wei Eric Wang, Chunyu Zeng
WNT pathways are critically involved in the cardiac hypertrophy growth. Porcupine, an acyltransferase that specifically enables secretion of all WNT ligands, became a highly druggable target for inhibiting WNT pathways. Here we test if a novel small-molecule porcupine inhibitor CGX1321, which has entered human clinical trials as an anti-cancer agent, exerts an anti-hypertrophic effect. Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy on four-month-old male C57 mice. Cardiac function was measured with echocardiography...
October 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30073927/exploring-proteomic-drug-targets-therapeutic-strategies-and-protein-protein-interactions-in-cancer-mechanistic-view
#15
Khalid Bashir Dar, Aashiq Hussain Bhat, Shajrul Amin, Syed Anjum, Bilal Ahmad Reshi, Mohammad Afzal Zargar, Akbar Masood, Showkat Ahmad Ganie
Protein-protein interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer...
August 2, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/30051493/wnt-receptor-frizzled-8-is-a-target-of-erg-in-prostate-cancer
#16
Balabhadrapatruni V S K Chakravarthi, Darshan S Chandrashekar, Sai Akshaya Hodigere Balasubramanya, Alyncia D Robinson, Shannon Carskadon, Uttam Rao, Jennifer Gordetsky, Upender Manne, George J Netto, Sunil Sudarshan, Nallasivam Palanisamy, Sooryanarayana Varambally
Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men. Many molecular changes have been detailed during PCa progression. The gene encoding the transcription factor ERG shows recurrent rearrangement, resulting in the overexpression of ERG in the majority of prostate cancers. Overexpression of ERG plays a critical role in prostate oncogenesis and development of metastatic disease. Among the downstream effectors of ERG, Frizzled family member FZD4 has been shown to be a target of ERG...
July 26, 2018: Prostate
https://www.readbyqxmd.com/read/30014891/antagonistic-role-of-klotho-derived-peptides-dynamics-in-the-pancreatic-cancer-treatment-through-obstructing-wnt-1-and-frizzled-binding
#17
Muhammad Fakhar, Najumuddin, Mehreen Gul, Sajid Rashid
Klotho is an anti-aging protein that is engaged in the suppression of canonical WNT signaling. In this study, we investigated the expression pattern of human WNTs and Klotho in the pancreatic cancer. In the cancerous cells, WNT-1 exhibited much higher expression as compared to other WNTs, while no WNT expression was detected in the normal tissue. In contrast, Klotho expression was significantly low in the cancerous tissue. Based on these observations, we intended to explore Klotho binding to WNT-1 and cystein-rich domains (CRDs) of Frizzled (FZD) homologs through molecular docking and dynamics simulation assays...
September 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/30008928/identification-and-validation-of-a-hedgehog-pathway-based-3-gene-prognostic-signature-for-gastric-cancers
#18
Jianbing Wu, Xi Wang, Wei Lu
Developing prognostic factors for patients with gastric cancer (GC) is crucial for the accurate identification of subgroups with distinct clinical outcomes and the development of effective treatment strategies. The aim of this study was to determine novel gene expression signatures from the hedgehog (Hh) signaling pathway as predictors of risk with biological significance. The Cancer Genome Atlas (TCGA) GC (STAD) cohort was used as the training dataset to select for significant prognostic Hh genes. Three Hh genes, indian hedgehog (IHH), patched 1 (PTCH1) and smoothened frizzled class receptor (SMO), were identified to be significant prognostic factors...
August 2018: Oncology Letters
https://www.readbyqxmd.com/read/29937983/selective-irreversible-inhibitors-of-the-wnt-deacylating-enzyme-notum-developed-by-activity-based-protein-profiling
#19
Radu M Suciu, Armand B Cognetta, Zachary E Potter, Benjamin F Cravatt
Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms. Aberrant Wnt signaling contributes to diseases such as cancer. Wnts are modified by an unusual O -fatty acylation event ( O -linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors. O -Palmitoleoylation of Wnts is introduced by the porcupine (PORCN) acyltransferase and removed by the serine hydrolase NOTUM. PORCN inhibitors are under development for oncology, while NOTUM inhibitors have potential for treating degenerative diseases...
June 14, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29928371/systematic-prediction-of-target-genes-and-pathways-in-cervical-cancer-from-microrna-expression-data
#20
Rui Chen, Yong-Hua Shi, Hong Zhang, Jian-Yun Hu, Yi Luo
Cervical cancer (CC) is a leading cause of cancer-associated mortality in women; thus, the present study aimed to investigated potential target genes and pathways in patients with CC by utilizing an ensemble method and pathway enrichment analysis. The ensemble method integrated a correlation method [Pearson's correlation coefficient (PCC)], a causal inference method (IDA) and a regression method [least absolute shrinkage and selection operator (Lasso)] using the Borda count election algorithm, forming the PCC, IDA and Lasso (PIL) method...
June 2018: Oncology Letters
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