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Long Cui, Juan Zhao, Jingjing Liu
BACKGROUND: Aberrant Wnt/β-catenin activation has been shown to play essential roles in cancer, including renal cell carcinoma (RCC). In this work, we demonstrate that Wnt/β-catenin inhibition by a Food and Drug Administration-approved drug, pyrvinium, effectively targets clear cell RCC and enhances chemotherapy agent's efficacy. MATERIALS AND METHODS: We performed in vitro cell culture assays and in vivo xenograft tumor model to evaluate the effects of pyrvinium alone and its combination with paclitaxel, and analyzed the underlying mechanism(s) of pyrvinium's action in RCC...
March 2018: American Journal of the Medical Sciences
Shirley Abitbol, Rajae Dahmani, Cédric Coulouarn, Bruno Ragazzon, Bernhard Mlecnik, Nadia Senni, Mathilde Savall, Pascale Bossard, Pierre Sohier, Valerie Drouet, Emilie Tournier, Florent Dumont, Romain Sanson, Julien Calderaro, Jessica Zucman-Rossi, Mireille Vasseur-Cognet, Pierre-Alexandre Just, Benoît Terris, Christine Perret, Hélène Gilgenkrantz
BACKGROUND & AIMS: The Wnt/β-catenin pathway is the most frequently deregulated pathway in hepatocellular carcinoma (HCC). Inactivating mutations of the gene encoding AXIN1, a known negative regulator of the Wnt/β-catenin signaling pathway, are observed in about 10% of HCCs. Whole-genome studies usually place HCC with AXIN1 mutations and CTNNB1 mutations in the group of tumors with Wnt/β-catenin activated program. However, it has been shown that HCCs with activating CTNNB1 mutations form a group of HCCs, with a different histology, prognosis and genomic signature to those with inactivating biallelic AXIN1 mutations...
March 7, 2018: Journal of Hepatology
Bingling Dai, Tianfeng Yang, Yujiao Ma, Nan Ma, Xianpeng Shi, Dongdong Zhang, Jie Zhang, Yanmin Zhang
Looking for novel, effective and less toxic therapies for cervical cancer is of significant importance. In this study, we reported that HMQ-T-F2(F2) significantly inhibited cell proliferation and transplantable tumour growth. Mechanistically, HMQ-T-F2 inhibited HeLa cell growth through repressing the expression and nuclear translocation of β-catenin, enhancing Axin expression, as well as downregulating the Wnt downstream targeted proteins. Knock-down of a checkpoint β-catenin by siRNA significantly attenuated HeLa cell proliferation...
March 7, 2018: Journal of Cellular and Molecular Medicine
Chen-Song Zhang, Mengqi Li, Yue Zong, Sheng-Cai Lin
Recent studies have revealed how AMPK is activated inside the cell and animal tissues: in response to low glucose, AXIN tethers LKB1, by virtue of their constitutive association, to AMPK located on the surface of late endosome/lysosome. Importantly, the lysosomal v-ATPase (vacuolar ATPase)-Ragulator complex, when primed by glucose starvation or concanamycin A, facilitates AXIN/LKB1 to interact with AMPK. Here, we describe the experimental procedures of the assays for detecting the translocation of AXIN/LKB1 or the assembly of the AXIN-based AMPK-activating complexes on the late endosome/lysosome...
2018: Methods in Molecular Biology
Dominic B Bernkopf, Kowcee Jalal, Martina Brückner, Karl X Knaup, Marc Gentzel, Alexandra Schambony, Jürgen Behrens
Mitochondrial abundance is dynamically regulated and was previously shown to be increased by Wnt/β-catenin signaling. Pgam5 is a mitochondrial phosphatase which is cleaved by the rhomboid protease presenilin-associated rhomboid-like protein (PARL) and released from membranes after mitochondrial stress. In this study, we show that Pgam5 interacts with the Wnt pathway component axin in the cytosol, blocks axin-mediated β-catenin degradation, and increases β-catenin levels and β-catenin-dependent transcription...
February 8, 2018: Journal of Cell Biology
Salim Ansari, Nicole Troelenberg, Van Anh Dao, Tobias Richter, Gregor Bucher, Martin Klingler
The distinction of anterior versus posterior is a crucial first step in animal embryogenesis. In the fly Drosophila, this axis is established by morphogenetic gradients contributed by the mother that regulate zygotic target genes. This principle has been considered to hold true for insects in general but is fundamentally different from vertebrates, where zygotic genes and Wnt signaling are required. We investigated symmetry breaking in the beetle Tribolium castaneum, which among insects represents the more ancestral short-germ embryogenesis...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ofelia Tacchelly-Benites, Zhenghan Wang, Eungi Yang, Hassina Benchabane, Ai Tian, Michael P Randall, Yashi Ahmed
The aberrant activation of Wnt signal transduction initiates the development of 90% of colorectal cancers, the majority of which arise from inactivation of the tumor suppressor Adenomatous polyposis coli (APC). In the classical model for Wnt signaling, the primary role of APC is to act, together with the concentration-limiting scaffold protein Axin, in a "destruction complex" that directs the phosphorylation and consequent proteasomal degradation of the transcriptional activator β-catenin, thereby preventing signaling in the Wnt-off state...
February 2018: PLoS Genetics
Zahid Khan, Maha Arafah, Jilani Purusottapatnam Shaik, Alka Mahale, Mohammad Saud Alanazi
Purpose: Breast carcinoma is the most common malignancy and leading cause of cancer-related deaths in women worldwide including Saudi Arabia. Breast cancer in Saudi women develops at a much early age with median age of onset of 49 years compared to 62 years observed in patients from USA. Aberrations in wingless and integration site growth factor (Wnt) signaling pathway have been pathologically implicated in development of breast cancers and hence its role was examined in Saudi patients...
2018: OncoTargets and Therapy
Dawei Wang, Guoliang Lu, Yuan Shao, Da Xu
Although prostate cancer can be surgical excised and effectively treated by androgen-deprivation therapy, radiotherapy, or chemotherapy, management of patients with advanced or drug-resistance prostate cancer stills remains a big trouble. Accumulated evidence indicated that miR-182 and Wnt/β-catenin function as tumor oncogene in the progression of a variety of tumors. However, little is known about how miR-182 regulates β-catenin signal molecular and impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of qRT-PCR, we found that prostate cancer tissues expressed much more miR-182 than non-cancer tissues did...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yang Yi, Jun Ma, Lu Jianrao, Hangqing Wang, Yingdan Zhao
CCN family, a group of six extracellular matrix-associated proteins, plays an important role in fibrosis. WISP3 has addressed as a pro-fibrotic molecule in the development of human lung fibrosis. However, whether WISP3 involved in the activation and proliferation of renal fibroblast, and ultimately inhibited fibroblast-myofibroblast transdifferentiation remained unknown. Herein, we found that down-regulated WISP3 was involved in the fibrogenesis of rat renal NRK-49F cells induced by transforming growth (TGF-β1), which was further confirmed in a rat renal fibrosis induced by unilateral ureteral obstruction (UUO)...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Patrick Unger, Kilian Neubert, Harry W Palm
A total of 35 common garfish, Belone belone (Linnaeus, 1761), were studied for metazoan parasites on their spawning grounds in the western Baltic Sea. Nine parasite species were found, and six new locality records could be established for German coastal waters (Axine belones, Monogenea; Proteocephalus sp., Cestoda; Anisakis simplex (s.s.), Contracaecum rudolphii A and Hysterothylacium aduncum, Nematoda; Echinorhynchus gadi, Acanthocephala). For the first time, the marine ectoparasite A. belones was recorded from the gills of garfish inside the Baltic Sea, indicating its ability to survive the spawning migration as well as the brackish water conditions at its reproduction grounds...
March 26, 2018: Acta Parasitologica
Fei Xing, Wen-Juan Yi, Fang Miao, Meng-Yun Su, Tie-Chi Lei
Baicalin is a traditional Chinese herbal medicine commonly used for hair loss, the precise molecular mechanism of which is unknown. In the present study, the mechanism of baicalin was investigated via the topical application of baicalin to reconstituted hair follicles on mice dorsa and evaluating the effect on canonical Wnt/β‑catenin signaling in the hair follicles and the activity of dermal papillar cells. The results indicate that baicalin stimulates the expression of Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein kinase 1α/adenomatous polyposis coli/glycogen synthase kinase 3β degradation complex, leading to accumulation of β‑catenin and activation of Wnt/β‑catenin signaling...
January 16, 2018: International Journal of Molecular Medicine
Glenda Comai, Agnès Boutet, Kristina Tanneberger, Filippo Massa, Ana-Sofia Rocha, Aurelie Charlet, Clara Panzolini, Fariba Jian Motamedi, Robert Brommage, Wolfgang Hans, Thomas Funck-Brentano, Martin Hrabe de Angelis, Christine Hartmann, Martine Cohen-Solal, Jürgen Behrens, Andreas Schedl
The X-linked WTX/AMER1 protein forms an important component of the β-catenin destruction complex that can both enhance and suppress canonical β-catenin signalling. Somatic mutations in WTX/AMER1 have been found in a proportion of the pediatric kidney cancer Wilms' tumour. By contrast, germline mutations cause the severe sclerosing bone dysplasia osteopathia striata congenita with cranial sclerosis (OSCS), a condition usually associated with fetal or perinatal lethality in male patients. Here we addressed the developmental and molecular function of WTX by generating two novel mouse alleles...
January 12, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Lei La, Lili Wang, Fei Qin, Jian Jiang, Songqi He, Chunxia Wang, Yuhao Li
ETHNOPHARMACOLOGICAL RELEVANCE: Zhen-wu-tang (ZWT), composed of Radix Aconiti lateralis, Rhizoma Atractylodis macrocephalae, Poria, Radix Paeoniae alba and ginger, is a classic Chinese herbal formula for the treatment of chronic kidney diseases that may cause chronic renal failure (CRF). AIM OF THE STUDY: To better understand its clinical use, this study investigated the effects and underlying mechanisms of action of ZWT on CRF. MATERIALS AND METHODS: CRF was induced by adenine...
December 14, 2017: Journal of Ethnopharmacology
Huiqiang Dou, Renhui Shen, Jianxin Tao, Longchang Huang, Haoze Shi, Hang Chen, Yixin Wang, Tong Wang
Curcumin exhibits anti-tumor effects in several cancers, including colorectal carcinoma (CRC), but the detailed mechanisms are still unclear. Here we studied the mechanisms underlying the anti-tumor effect of curcumin in colon cancer cells. SW480 cells were injected into mice to establish the xenograft tumor model, followed by evaluation of survival rate with the treatment of curcumin. The expression levels of β-catenin, Axin and TCF4 were measured in the SW480 cells in the absence or presence of curcumin...
2017: Frontiers in Pharmacology
Xiaofeng Han, Xinfeng Li, Guibin Zhong, Zude Liu
Bone marrow mesenchymal stem cells (BMSCs) are stem cells with multidirectional differentiation potential, which can be used as seed cells to repair and reconstruct many types of tissues and organs following injury or disease. Osteogenic differentiation involves a variety of pathway and factors, including cytokines, growth factors, and hormones. In the present study, we investigated the potential role of Dishevelled in osteogenic differentiation of BMSCs in induction medium containing the methyltransferase inhibitor 5-aza-2'-deoxycytidine...
2017: American Journal of Translational Research
Abigail S Tucker, Carlene J Dyer, Juan M Fons Romero, Tathyane H N Teshima, Jennifer C Fuchs, Hannah Thompson
The middle ear epithelium is derived from neural crest and endoderm, which line distinct regions of the middle ear cavity. Here, we investigate the distribution of putative stem cell markers in the middle ear, combined with an analysis of the location of label-retaining cells (LRCs) to create a map of the middle ear mucosa. We show that proliferating cells and LRCs were associated with specific regions of the ear epithelium, concentrated in the hypotympanum at the base of the auditory bulla and around the ear drum...
January 11, 2018: Development
Ata Ur Rahman Mohammed Abdul, Bhagya De Silva, Ronald K Gary
Lithium salt is a classic glycogen synthase kinase 3 (GSK3) inhibitor. Beryllium is a structurally related inhibitor that is more potent but relatively uncharacterized. This study examined the effects of these inhibitors on the phosphorylation of endogenous GSK3 substrates. In NIH-3T3 cells, both salts caused a decrease in phosphorylated glycogen synthase, as expected. GSK3 inhibitors produce enhanced phosphorylation of Ser9 of GSK3β via a positive feedback mechanism, and both salts elicited this enhancement...
January 26, 2018: Biology Open
Shengliang He, Jing Du, Fangqi Liu
Familial adenomatous polyposis (FAP) is one of the most common hereditary colorectal cancers. Its intestinal and extra-intestinal manifestations are correlated with mutation sties of the APC gene. Potential gene modulation sites in patients who have typical clinical manifestations but with unidentified APC mutations are also discussed, which included MUTYH gene, AXIN gene and certain epigenetic changes. With the generalization of Precision Medicine, to offer individualized treatment and surveillance strategy based on the genotype-phenotype correlation will be of great value for FAP patients...
December 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Ye Wu, Ye-Hua Li, Xiang Li, Yan Zou, Hong-Li Liao, Lei Liu, Ye-Guang Chen, Donald Bierer, Hong-Gang Hu
The all-hydrocarbon peptide stapling strategy has recently been extensively explored in drug discovery. There remains the potential for improvement regarding the retention of the amino acid side chains at the stapled positions. Herein, we describe a new series of amino acids that not only contain the native side chains, but also carry the alkenyl arms that are needed for the ring-closing stapling chemistry. We incorporate the new amino acids into a β-catenin-binding domain of Axin (469-482) and develop a new category of stapled peptides with the retention of the native side chains...
November 1, 2017: Chemical Science
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