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https://www.readbyqxmd.com/read/28431932/zbed3-as1-induces-chondrogenesis-of-human-synovial-fluid-mesenchymal-stem-cells
#1
Farong Ou, Kai Su, Jiadong Sun, Wenting Liao, Yu Yao, Youhua Zheng, Zhiguang Zhang
Human synovial fluid-derived mesenchymal stem cells (SFMSCs) have great potential for cartilage induction and are promising for cell-based strategies for articular cartilage repair. Many long non-coding RNAs (lncRNAs) regulate chondrogenesis of MSCs. We hypothesized that the divergent lncRNA ZBED3-AS1, which binds locally to chromatin, could promote the expression of zbed3, a novel Axin-interacting protein that activates Wnt/β-catenin signaling, involved in chondrogenesis. However, the function of ZBED3-AS1 in SFMSCs is unclear...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28430866/maternal-high-sucrose-diets-altered-vascular-large-conductance-ca2-activated-k-channels-via-reactive-oxygen-species-in-offspring-rats%C3%A2
#2
Xueqin Feng, Xiuwen Zhou, Wenna Zhang, Xiang Li, Axin He, Bailin Liu, Ruixiu Shi, Lei Wu, Jue Wu, Di Zhu, Na Li, Miao Sun, Zhice Xu
Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high-sucrose (HS). We found that prenatal high-sucrose diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430656/thyroid-cancer-1-c8orf4-shows-high-expression-no-mutation-and-reduced-methylation-level-in-lung-cancers-and-its-expression-correlates-with-%C3%AE-catenin-and-dnmt1-expression-and-poor-prognosis
#3
Yi-Wen Zheng, Li Zhang, Yuan Wang, Song-Yan Chen, Lei Lei, Na Tang, Da-Lei Yang, Lin-Lin Bai, Xiu-Peng Zhang, Gui-Yang Jiang, Lian-He Yang, Hong-Tao Xu, Qing-Chang Li, Xue-Shan Qiu, En-Hua Wang
Thyroid cancer 1 (TC1, C8orf4) plays important roles in tumors. The aim of this study was to examine the protein expression levels, methylation status, and mutational status of TC1 (C8orf4) in lung cancers, and investigate the correlation between TC1, other members of the Wnt signaling pathway, and lung cancer. TC1 expression levels were assessed via immunohistochemical staining in 179 cases of lung cancer. β-catenin, TCF4, Axin, Disabled-2, Chibby, and DNA methyltransferase-1 (DNMT1) expressions were also examined...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430615/a-novel-mechanism-of-angiotensin-ii-regulated-placental-vascular-tone-in-the-development-of-hypertension-in-preeclampsia
#4
Qinqin Gao, Jiaqi Tang, Na Li, Xiuwen Zhou, Yongmei Li, Yanping Liu, Jue Wu, Yuxian Yang, Ruixiu Shi, Axin He, Xiang Li, Yingying Zhang, Jie Chen, Lubo Zhang, Miao Sun, Zhice Xu
The present study tested the hypothesis that angiotensin II plays a role in the regulation of placental vascular tone, which contributes to hypertension in preeclampsia. Functional and molecular assays were performed in large and micro placental and non-placental vessels from humans and animals. In human placental vessels, angiotensin II induced vasoconstrictions in 78.7% vessels in 155 tests, as referenced to KCl-induced contractions. In contrast, phenylephrine only produced contractions in 3.0% of 133 tests...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429652/atypical-regulators-of-wnt-%C3%AE-catenin-signaling-as-potential-therapeutic-targets-in-hepatocellular-carcinoma
#5
Jianxiang Chen, Muthukumar Rajasekaran, Kam M Hui
Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28418865/anti-helminthic-niclosamide-inhibits-ras-driven-oncogenic-transformation-via-activation-of-gsk-3
#6
Sung Yong Ahn, Ji Hye Yang, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Jun Seop Yun, Hee Eun Kang, Yoonmi Lee, Jiwon Choi, Hyun Sil Kim, Jong In Yook
Despite the importance of Ras oncogenes as a therapeutic target in human cancer, their 'undruggable' tertiary structures limit the effectiveness of anti-Ras drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent degradation. In the accompanying report, we show that the anti-helminthic niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer cells, with reversion of Snail-mediated epithelial-mesenchymal transition...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418862/niclosamide-is-a-potential-therapeutic-for-familial-adenomatosis-polyposis-by-disrupting-axin-gsk3-interaction
#7
Sung Yong Ahn, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Ji Hye Yang, So Young Cha, Eunae Sandra Cho, Yoonmi Lee, Jeong Seok Cha, Hyun Soo Cho, Yoon Jeon, Young-Su Yuk, Suebean Cho, Kyoung Tai No, Hyun Sil Kim, Ho Lee, Jiwon Choi, Jong In Yook
The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling and EMT comprises an attractive therapeutic strategy, molecular targets for small molecules reverting Wnt and EMT have not been widely studied. Meanwhile, the anti-helminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418856/low-density-lipoprotein-receptor-related-protein-6-is-a-novel-coreceptor-of-protease-activated-receptor-2-in-the-dynamics-of-cancer-associated-%C3%AE-catenin-stabilization
#8
Jeetendra Kumar Nag, Arun Kancharla, Myriam Maoz, Hagit Turm, Daniel Agranovich, Chhedi Lal Gupta, Beatrice Uziely, Rachel Bar-Shavit
Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the molecular machinery of PAR2-instigated tumors remains to be elucidated. We show that PAR2 is a potent inducer of β-catenin stabilization, a core process in cancer biology, leading to its transcriptional activity. Novel association of low-density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds (Fz), with PAR2 takes place following PAR2 activation. The association between PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence resonance energy transfer (BRET), and confocal microscopy analysis...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408316/down-regulation-of-lrp1b-in-colon-cancer-promoted-the-growth-and-migration-of-cancer-cells
#9
Zhiqiang Wang, Peng Sun, Chun Gao, Ji Chen, Jun Li, Zhonghao Chen, Ming Xu, Jun Shao, Yunpeng Zhang, Jiang Xie
Aberrant activation of beta-catenin/TCF signaling is one of the hallmarks of colon cancer. It is of great interest to study the mechanism for the regulation of beta-catenin/TCF signaling. In this study, it was found that LRP1B was down-regulated in colon cancer tissues and inhibited the growth, migration and metastasis of colon cancer cells. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling...
April 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28371398/targeting-tankyrase-to-fight-wnt-dependent-tumours
#10
Tor Espen Thorvaldsen
Aberrant WNT signalling activity is linked to various diseases due to the WNT dependency of fundamental processes during development and in adult tissue homeostasis. Mutations in components of the multiprotein β-catenin destruction complex promote excessive amounts of the main transcriptional activator β-catenin and are particularly common in colorectal cancer (CRC). The tankyrase enzymes were recently implicated as negative regulators of destruction complex activity by mediating degradation of the scaffolding protein AXIN...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28355271/transient-helicity-in-intrinsically-disordered-axin-1-studied-by-nmr-spectroscopy-and-molecular-dynamics-simulations
#11
Rainer Bomblies, Manuel Patrick Luitz, Sandra Scanu, Tobias Madl, Martin Zacharias
Many natural proteins are, as a whole or in part, intrinsically disordered. Frequently, such intrinsically disordered regions (IDRs) undergo a transition to a defined and often helical conformation upon binding to partner molecules. The intrinsic propensity of an IDR sequence to fold into a helical conformation already in the absence of a binding partner can have a decisive influence on the binding process and affinity. Using a combination of NMR spectroscopy and molecular dynamics (MD) simulations we have investigated the tendency of regions of Axin-1, an intrinsically disordered scaffolding protein of the WNT signaling pathway, to form helices in segments interacting with binding partners...
2017: PloS One
https://www.readbyqxmd.com/read/28292937/disruption-of-tcf-%C3%AE-catenin-binding-impairs-wnt-signalling-and-induces-apoptosis-in-soft-tissue-sarcoma-cells
#12
Esther Martinez-Font, Irene Felipe-Abrio, Silvia Calabuig-Fariñas, Rafael F Ramos, Josefa Terrasa, Oliver Vögler, Regina Alemany, Javier Martín-Broto, Antònia Obrador-Hevia
Soft tissue sarcomas (STS) are malignant tumours of mesenchymal origin and represent around 1% of adult cancers, being a very heterogeneous group of tumours with more than 50 different subtypes. The Wnt signalling pathway is involved in the development and in the regulation, self-renewal and differentiation of mesenchymal stem cells and plays a role in sarcomagenesis. In this study we have tested pharmacological inhibition of Wnt signalling mediated by disruption of TCF/β-catenin binding and AXIN stabilization, being the first strategy more efficient in reducing cell viability and downstream effects...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28285186/inflammatory-markers-in-late-pregnancy-in-association-with-postpartum-depression-a-nested-case-control-study
#13
Emma Bränn, Fotios Papadopoulos, Emma Fransson, Richard White, Åsa Edvinsson, Charlotte Hellgren, Masood Kamali-Moghaddam, Adrian Boström, Helgi B Schiöth, Inger Sundström-Poromaa, Alkistis Skalkidou
Recent studies indicate that the immune system adaptation during pregnancy could play a significant role in the pathophysiology of perinatal depression. The aim of this study was to investigate if inflammation markers in a late pregnancy plasma sample can predict the presence of depressive symptoms at eight weeks postpartum. Blood samples from 291 pregnant women (median and IQR for days to delivery, 13 and 7-23days respectively) comprising 63 individuals with postpartum depressive symptoms, as assessed by the Edinburgh postnatal depression scale (EPDS≥12) and/or the Mini International Neuropsychiatric Interview (M...
February 28, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28276699/p120-catenin-in-canonical-wnt-signaling
#14
Mireia Duñach, Beatriz Del Valle-Pérez, Antonio García de Herreros
Canonical Wnt signaling controls β-catenin protein stabilization, its translocation to the nucleus and the activation of β-catenin/Tcf-4-dependent transcription. In this review, we revise and discuss the recent results describing actions of p120-catenin in different phases of this pathway. More specifically, we comment its involvement in four different steps: (i) the very early activation of CK1ɛ, essential for Dvl-2 binding to the Wnt receptor complex; (ii) the internalization of GSK3 and Axin into multivesicular bodies, necessary for a complete stabilization of β-catenin; (iii) the activation of Rac1 small GTPase, required for β-catenin translocation to the nucleus; and (iv) the release of the inhibitory action caused by Kaiso transcriptional repressor...
March 3, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28271271/a-kinetic-model-to-study-the-regulation-of-formula-see-text-catenin-apc-and-axin-in-the-human-colonic-crypt
#15
Brooks Emerick, Gilberto Schleiniger, Bruce M Boman
The Wnt/[Formula: see text]-catenin pathway plays a crucial role in stem cell renewal and differentiation in the normal human colonic crypt. The balance between [Formula: see text]-catenin and APC along the crypt axis determines its normal functionality. The mechanism that deregulates this balance may give insight into the initiation of colorectal cancer. This is significant because the spatial dysregulation of [Formula: see text]-catenin by the mutated tumor suppressor gene/protein APC in human colonic crypts is responsible for the initiation and growth of colorectal cancer...
March 7, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28260089/overexpression-of-mir%C3%A2-214-promotes-the-progression-of-human-osteosarcoma-by-regulating-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway
#16
Xun-Bing Zhu, Zhong-Chuan Zhang, Guan-Sheng Han, Jun-Zhu Han, Da-Peng Qiu
The aberrant expression of microRNA (miR)‑214 contributes to the regulation of normal and cancer cell biology, and is associated with human malignancies, however, it can operate in a contradictory manner. The role of miR‑214 in osteosarcoma remains to be fully elucidated. The aim of the present study was to investigate the effects of miR‑214 on osteosarcoma progression and tumor cell proliferation, and examine the molecular mechanism underlying osteosarcoma. The level of miR‑214 was determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis in osteosarcoma and matched paracancerous tissues, and in human osteosarcoma cancer cell lines...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28253973/methods-to-study-lysosomal-ampk-activation
#17
C-S Zhang, M Li, S-C Lin
The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis. It is activated by the upstream kinase LKB1 (liver kinase B1) when the AMP/ATP ratio is increased during starvation or heightened exercises. Based on reconstitution experiments using purified individual proteins, AMPK was demonstrated to be directly phosphorylated on its conserved residue Thr172 by LKB1, which was promoted by increased levels of AMP. However, recent studies have engendered a paradigm shift for how AMPK is activated inside the cell or animal tissues, unraveling that AXIN binds to LKB1 and tethers it to AMPK located on the surface of late endosome and lysosome (hereafter, only lysosome is discussed) in response to glucose starvation...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#18
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28212537/itraconazole-exerts-its-anti-melanoma-effect-by-suppressing-hedgehog-wnt-and-pi3k-mtor-signaling-pathways
#19
Guanzhao Liang, Musang Liu, Qiong Wang, Yongnian Shen, Huan Mei, Dongmei Li, Weida Liu
Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate cancer, and non-small cell lung cancer. Whether itraconazole has any specific anti-tumor effect on melanoma remains unknown. However, the goal of this study is to investigate the effect of itraconazole on melanoma and to reveal some details of its underlying mechanism. In the in vivo xenograft mouse model, we find that itraconazole can inhibit melanoma growth and extend the survival of melanoma xenograft mice, compared to non-itraconazole-treated mice...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179481/apc-mutations-as-a-potential-biomarker-for-sensitivity-to-tankyrase-inhibitors-in-colorectal-cancer
#20
Noritaka Tanaka, Tetsuo Mashima, Anna Mizutani, Ayana Sato, Aki Aoyama, Bo Gong, Haruka Yoshida, Yukiko Muramatsu, Kento Nakata, Masaaki Matsuura, Ryohei Katayama, Satoshi Nagayama, Naoya Fujita, Yoshikazu Sugimoto, Hiroyuki Seimiya
In most colorectal cancers (CRCs), Wnt/β-catenin signaling is activated by loss-of-function mutations in the adenomatous polyposis coli (APC) gene and plays a critical role in tumorigenesis. Tankyrases poly(ADP-ribosyl)ate and destabilize Axins, a negative regulator of β-catenin, and upregulate β-catenin signaling. Tankyrase inhibitors downregulate β-catenin and are expected to be promising therapeutics for CRC. However, CRC cells are not always sensitive to tankyrase inhibitors, and predictive biomarkers for the drug sensitivity remain elusive...
February 8, 2017: Molecular Cancer Therapeutics
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