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frizzled cancer

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
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
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
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. Four-month-old male C57 mice were used in the experiments. Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy in-vivo...
August 1, 2018: Biochimica et Biophysica Acta
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
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
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
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
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
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
Lu Zhang, Cuihua Feng, Yamin Zhou, Qiong Zhou
The present study aimed to identify bladder cancer-associated microRNAs (miRNAs) and target genes, and further analyze the potential molecular mechanisms involved in bladder cancer. The mRNA and miRNA expression profiling dataset GSE40355 was downloaded from the Gene Expression Omnibus database. The Limma package in R was used to identify differential expression levels. The Human microRNA Disease Database was used to identify bladder cancer-associated miRNAs and Target prediction programs were used to screen for miRNA target genes...
June 2018: Oncology Letters
Yang Chen, Fan Zhang, Yawei Zhao, Kan He, Xiao Zheng, Yue Pan, Dan Shao, Pei Shang, Yongsheng Yang, Dan Zhang, Yingjun Xie, Xiaoxiao Yao, Li Chen, Jing Li, Xuewen Zhang
Background: Obesity was a recognized risk factor for the development and progression of hepatocellular carcinoma (HCC). However, the effects and mechanisms by which obesity promotes HCC metastasis remain poorly understood. Materials and methods: We cultured adipocyte induced by preadipocyte 3T3-L1 in vitro and established HCC metastasis model in obesity mouse in vivo to mimic the tumor microenvironment in obese status. The mechanisms underlying obesity-associated miR-27a upregulation promoting HCC metastasis were investigated...
2018: OncoTargets and Therapy
Madhulaxmi Marimuthu, Manoharan Andiappan, Abdul Wahab, M R Muthusekhar, Anandan Balakrishnan, Sambandham Shanmugam
Aim: The aim of this study is to explore the prognostic significance and clinicopathological correlations of the Wnt pathway genes in a cohort of surgically treated patients with oral squamous cell carcinoma (OSCC) patients. Settings and Design: A prospective genetic study on patients with OSCC was carried out during the period from July 2014 to January 2016. Informed consent from patients and institutional ethical approval for the study was obtained and the guidelines were strictly followed for collection of samples...
May 2018: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
Kun Han, Tingyuan Lang, Zhiqi Zhang, Yi Zhang, Yongning Sun, Zan Shen, Roger W Beuerman, Lei Zhou, Daliu Min
The mechanisms underlying luteolin-induced inhibition of prostate cancer (PCa) stemness have remained elusive. Here, we report that luteolin suppresses PCa stemness through Wnt signaling by upregulation of FZD6 (frizzled class receptor 6). Luteolin inhibits PCa cell proliferation, migration, self-renewal as well as the expression of prostate cancer stem cell markers in vitro. Through iTRAQ-based quantitative proteomics study, we identified 208 differentially expressed proteins in luteolin-treated PC-3 cells...
June 4, 2018: Scientific Reports
Hanin Alamir, Mona Alomari, Abdulla Ahmed A Salwati, Mohamad Saka, Mohammed Bangash, Saleh Baeesa, Fahad Alghamdi, Angel Carracedo, Hans-Juergen Schulten, Adeel Chaudhary, Adel Abuzenadah, Deema Hussein
Background: Meningioma cancer stem cells (MCSCs) contribute to tumor aggressiveness and drug resistance. Successful therapies developed for inoperable, recurrent, or metastatic tumors must target these cells and restrict their contribution to tumor progression. Unfortunately, the identity of MCSCs remains elusive, and MSCSs' in situ spatial distribution, heterogeneity, and relationship with tumor grade, remain unclear. Methods: Seven tumors classified as grade II or grade III, including one case of metastatic grade III, and eight grade I meningioma tumors, were analyzed for combinations of ten stem cell (SC)-related markers using immunofluorescence of consecutive sections...
2018: Cancer Cell International
Chao-Ping Wang, Teng-Hung Yu, Cheng-Ching Wu, Wei-Chin Hung, Chia-Chang Hsu, I-Ting Tsai, Wei-Hua Tang, Fu-Mei Chung, Jer-Yiing Houng, Yau-Jiunn Lee, Yung-Chuan Lu
Secreted frizzled-related protein-5 (Sfrp5) known as secreted antagonist binds to Wnt protein. It has been shown to be downregulated by histone acetylation and promoter methylation, and to function as a tumor suppressor gene by inducing apoptosis in renal cell cancer cells. However, its relationship with chronic kidney disease (CKD) has not been well studied. Our objective was to investigate the effect of plasma Sfrp5 levels in subjects with and without CKD. Plasma Sfrp5 levels were determined by enzyme-linked immunosorbent assays in 196 consecutive patients with acute ST-segment elevation myocardial infarction (STEMI)...
May 25, 2018: Cytokine
Chui-Mian Zeng, Zhe Chen, Li Fu
Frizzled receptors (FZDs) are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs) that serve as receptors for secreted Wingless-type (WNT) ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs...
May 22, 2018: International Journal of Molecular Sciences
Sohei Kitazawa, Ryuma Haraguchi, Riko Kitazawa
Cytosine methylation plays a major role in the regulation of sequential and tissue-specific expression of genes. De novo aberrant DNA methylation and demethylation are also crucial processes in tumorigenesis and tumor progression. The mechanisms of how and when such aberrant methylation and demethylation occur in tumor cells are still obscure, however. To evaluate subtle epigenetic alteration among minor subclonal populations, morphology-oriented epigenetic analysis is requisite, especially where heterogeneity and flexibility are as notable as in the process of cancer progression and cellular differentiation at critical stages...
July 2018: Histochemistry and Cell Biology
Virginia Murillo-Garzón, Irantzu Gorroño-Etxebarria, Malin Åkerfelt, Mikael Christer Puustinen, Lea Sistonen, Matthias Nees, James Carton, Jonathan Waxman, Robert M Kypta
Wnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription...
May 1, 2018: Nature Communications
Zhongchuan Wang, Rujia Li, Yongshan He, Shiyong Huang
Background: Secreted frizzled-related protein 1 (SFRP1) is a member of the SFRPs family that modulates the Wnt signal transduction pathway. Recent studies have showed down-regulation of SFRP1 expression in colorectal cancer (CRC). We aimed to evaluate the effect of SFRP1 on the proliferation, migration, invasion and apoptosis of CRC cells in vitro. Materials and methods: We used real-time fluorescence quantification (RT-PCR) and Western blotting to detect SFRP1 expression in CRC, pericarcinomatous tissues and CRC cell lines...
2018: Cancer Cell International
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