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frizzled cancer

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
Fouad Saeg, Muralidharan Anbalagan
Breast cancer is a heterogeneous disease that accounts for 30% of all cancers diagnosed in women and over half a million deaths per year. Cancer stem cells (CSCs) make up a small subpopulation of cells within a tumor, are capable of self-renewal and, are responsible for tumor initiation, formation, and recurrence. Breast CSCs (BCSCs) have been the subject of concentrated research as potential targets for breast cancer therapies. Cell surface markers CD44+/CD24- have been established as minimum biomarkers for BCSCs and the upregulation of CD44 expression has been linked to tumor formation in numerous cancers...
2018: Stem Cell Investigation
Eda Becer, Duygu Yiğit Hanoğlu, Hilal Kabadayı, Azmi Hanoğlu, Seda Vatansever, Dudu Özkum Yavuz, Filiz Meriçli, Ali Hikmet Meriçli
OBJECTIVE: Colchicum pusillum belongs to the family Colchicaceae that particularly rich in tropolonic alkaloids. The aim of this study was to investigate the cytotoxicity and in vitro anticancer activity of Colchicum pusillum ethanolic extract on Colo-320 primer and Colo-741 metastatic colon adenocarcinoma cell lines. MATERIALS AND METHODS: Colchicum pusillum was collected and extracted with ethanol. Different concentrations of Colchicum pusillum extract were incubated for 24 h and 48 h with Colo-320 and Colo-741 cells...
November 17, 2018: Gene
Yu-Heng Vivian Ma, Liangcheng Xu, Xueting Mei, Kevin Middleton, Lidan You
Bone metastases occur in 65% to 75% of patients with advanced breast cancer and significantly worsen their survival and quality of life. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced the transendothelial migration of breast cancer cells. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels...
November 11, 2018: Journal of Cellular Biochemistry
Haochang Hu, Tiangong Wang, Ranran Pan, Yong Yang, Bin Li, Cong Zhou, Jun Zhao, Yi Huang, Shiwei Duan
Colorectal cancer (CRC) is one of the leading causes of death worldwide. Aberrant DNA methylation has been recognized as one of the most common molecular alterations in CRC. The goal of this study was to investigate the diagnostic value of SFRP1 and SFRP2 methylation for CRC. A total of 80 pairs of CRC patients were recruited to test the association of SFRP1 and SFRP2 promotor methylation with CRC. Methylation assay was performed using quantitative methylation-specific polymerase chain reaction (qMSP) method...
October 27, 2018: Pathology Oncology Research: POR
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
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...
December 2018: Trends in Biochemical Sciences
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
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
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
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
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
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
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
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 low-density-lipoprotein 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 (SFRP) and dickkopf-related protein (DKK), play a critical role in embryo development and adult homeostasis. Overactivation of Wnt signaling has been implicated in some human diseases including cancer...
November 2018: Cancer Science
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...
October 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. 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
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
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