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https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28153722/inhibition-of-dixdc1-by-microrna-1271-suppresses-the-proliferation-and-invasion-of-prostate-cancer-cells
#4
Jiateng Zhong, Yufei Liu, Qingli Xu, Jian Yu, Muchun Zhang
Disheveled-Axin domain containing 1 (DIXDC1) is involved in the development and progression of multiple cancers. However, the function significance of DIXDC1 in prostate cancer remains unclear. In this study, we investigated the function of DIXDC1 in prostate cancer and the regulation of DIXDC1 by microRNAs (miRNAs). We found that DIXDC1 was highly expressed in prostate cancer cells. Knockdown of DIXDC1 by small interfering RNAs markedly suppressed proliferation, invasion and Wnt signaling in prostate cancer cells...
January 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28137581/wnt-%C3%AE-catenin-pathway-modulates-the-tnf-%C3%AE-induced-inflammatory-response-in-bronchial-epithelial-cells
#5
Jaewoong Jang, Yoonju Jung, Seyeon Chae, Sang-In Chung, Seok-Min Kim, Yoosik Yoon
In this study, TNF-α was found to activate the WNT/β-catenin pathway in BEAS-2B human bronchial epithelial cells. Levels of phospho-LRP6, Dvl-2, and phospho-GSK-3β were elevated, while that of Axin was reduced by TNF-α treatment. Nuclear translocation of β-catenin and the reporter activity of a β-catenin-responsive promoter were increased by TNF-α treatment. Under the same experimental conditions, TNF-α activated the NF-κB signaling, which includes the phosphorylation and degradation of IκB and nuclear translocation and target DNA binding of NF-κB, and it was found that an inhibitor of NF-κB activation, JSH-23, inhibited TNF-α-induced Wnt signaling as well as NF-κB signaling...
January 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28133948/maternal-high-salt-diet-altered-adenosine-mediated-vasodilatation-via-pka-bkchannel-pathway-in-offspring-rats
#6
Jue Wu, Na Li, Yanping Liu, Weisheng Li, Axin He, Di Zhu, Xueqin Feng, Bailin Liu, Ruixiu Shi, Yujuan Zhang, Juanxiu Lv, Zhice Xu
SCOPE: High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via PKA pathway in coronary arteries. METHODS AND RESULTS: Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K(+) channels and Adenosine signal pathways...
January 29, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28129128/aptamer-targeted-attenuation-of-il-2-signaling-in-cd8-t-cells-enhances-antitumor-immunity
#7
Anugraha Rajagopalan, Alexey Berezhnoy, Brett Schrand, Yvonne Puplampu-Dove, Eli Gilboa
Immune responses elicited against cancer using existing therapies such as vaccines or immune stimulatory antibodies are often not curative. One way to potentiate antitumor immunity is to enhance the long-term persistence of anti-tumor CD8(+) T cells. Studies have shown that the persistence of activated CD8(+) T cells is negatively impacted by the strength of interleukin 2 (IL-2) signaling. Here, we used small interfering RNAs (siRNAs) against CD25 (IL-2Rα) to attenuate IL-2 signaling in CD8(+) T cells. The siRNAs were targeted to 4-1BB-expressing CD8(+) T cells by conjugation to a 4-1BB-binding oligonucleotide aptamer...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28107521/differential-roles-of-axin1-and-axin2-in-tankyrase-inhibitor-induced-formation-of-degradasomes-and-%C3%AE-catenin-degradation
#8
Tor Espen Thorvaldsen, Nina Marie Pedersen, Eva Maria Wenzel, Harald Stenmark
Inhibition of the tankyrase enzymes (TNKS1 and TNKS2) has recently been shown to induce highly dynamic assemblies of β-catenin destruction complex components known as degradasomes, which promote degradation of β-catenin and reduced Wnt signaling activity in colorectal cancer cells. AXIN1 and AXIN2/Conductin, the rate-limiting factors for the stability and function of endogenous destruction complexes, are stabilized upon TNKS inhibition due to abrogated degradation of AXIN by the proteasome. Since the role of AXIN1 versus AXIN2 as scaffolding proteins in the Wnt signaling pathway still remains incompletely understood, we sought to elucidate their relative contribution in the formation of degradasomes, as these protein assemblies most likely represent the morphological and functional correlates of endogenous β-catenin destruction complexes...
2017: PloS One
https://www.readbyqxmd.com/read/28106087/dynamical-states-possibilities-and-propagation-of-stress-signal
#9
Md Zubbair Malik, Shahnawaz Ali, Soibam Shyamchand Singh, Romana Ishrat, R K Brojen Singh
The stress driven dynamics of Notch-Wnt-p53 cross-talk is subjected to a few possible dynamical states governed by simple fractal rules, and allowed to decide its own fate by choosing one of these states which are contributed from long range correlation with varied fluctuations due to active molecular interaction. The topological properties of the networks corresponding to these dynamical states have hierarchical features with assortive structure. The stress signal driven by nutlin and modulated by mediator GSK3 acts as anti-apoptotic signal in this system, whereas, the stress signal driven by Axin and modulated by GSK3 behaves as anti-apoptotic for a certain range of Axin and GSK3 interaction, and beyond which the signal acts as favor-apoptotic signal...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090074/targeting-of-wnt-%C3%AE-catenin-by-anthelmintic-drug-pyrvinium-enhances-sensitivity-of-ovarian-cancer-cells-to-chemotherapy
#10
Chongyuan Zhang, Zhenge Zhang, Shuirong Zhang, Wenrong Wang, Ping Hu
BACKGROUND Aberrant activation of Wnt/β-catenin has been shown to promote ovarian cancer proliferation and chemoresistance. Pyrvinium, an FDA-approved anthelmintic drug, has been identified as a potent Wnt inhibitor. Pyrvinium may sensitize ovarian cancer cells to chemotherapy. MATERIAL AND METHODS The effect of pyrvinium alone and its combination with paclitaxel in ovarian cancer was investigated using an in vitro culture system and in vivo xenograft models. The mechanisms of its action were also analyzed, focusing on the Wnt/β-catenin pathway...
January 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27959917/dual-roles-for-membrane-association-of-drosophila-axin-in-wnt-signaling
#11
Zhenghan Wang, Ofelia Tacchelly-Benites, Eungi Yang, Yashi Ahmed
Deregulation of the Wnt signal transduction pathway underlies numerous congenital disorders and cancers. Axin, a concentration-limiting scaffold protein, facilitates assembly of a "destruction complex" that prevents signaling in the unstimulated state and a plasma membrane-associated "signalosome" that activates signaling following Wnt stimulation. In the classical model, Axin is cytoplasmic under basal conditions, but relocates to the cell membrane after Wnt exposure; however, due to the very low levels of endogenous Axin, this model is based largely on examination of Axin at supraphysiological levels...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27852897/reconstituting-regulation-of-the-canonical-wnt-pathway-by-engineering-a-minimal-%C3%AE-catenin-destruction-machine
#12
Mira I Pronobis, Natalie Deuitch, Vinya Posham, Yuko Mimori-Kiyosue, Mark Peifer
Negatively regulating key signaling pathways is critical to development and altered in cancer. Wnt signaling is kept off by the destruction complex, which is assembled around the tumor suppressors APC and Axin and targets β-catenin for destruction. Axin and APC are large proteins with many domains and motifs that bind other partners. We hypothesized that if we identified the essential regions required for APC:Axin cooperative function and used these data to design a minimal β-catenin-destruction machine, we would gain new insights into the core mechanisms of destruction complex function...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27852210/axin-ppi-networks-new-interacting-proteins-and-new-targets
#13
Xiaomin Song, Wenwen Cai, Lin Li
The scaffold protein Axin plays important roles in multiple signaling pathways through mediating the formation of different signaling complexes. Axin is best known for its role as a negative regulator in Wnt/β-catenin pathway. Aberrant activation of the key components in Wnt/β-catenin pathway including Axin has been linked to a variety of human cancers. Drugs developed for this pathway are far from satisfying largely due to the limited targets especially enzymesin this pathway. Almost all Axinsignal pathways depend on a number of protein-protein interactions (PPIs) for transmitting information, making PPIs attractive targets and probably a future direction for drug discovery...
2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27851961/wip-drives-tumor-progression-through-yap-taz-dependent-autonomous-cell-growth
#14
Ricardo Gargini, Maribel Escoll, Esther García, Ramón García-Escudero, Francisco Wandosell, Inés María Antón
In cancer, the deregulation of growth signaling pathways drives changes in the cell's architecture and its environment that allow autonomous growth of tumors. These cells then acquire a tumor-initiating "stemness" phenotype responsible for disease advancement to more aggressive stages. Here, we show that high levels of the actin cytoskeleton-associated protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are linked to the tumor-initiating cell phenotype. We find that WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27705813/axin-shapes-tankyrase-architecture
#15
Sebastian Guettler
The poly(ADP-ribose)polymerase (PARP) Tankyrase uses ankyrin repeat modules to capture substrates via Tankyrase-binding peptide motifs. In this issue of Structure, Eisemann et al. (2016) describe how the signaling protein AXIN can access and conformationally adapt the multivalent ankyrin repeat region of Tankyrase and discuss potential implications for enzymatic substrate modification.
October 4, 2016: Structure
https://www.readbyqxmd.com/read/27630299/axin1-expression-and-localization-in-meningiomas-and-association-to-changes-of-apc-and-e-cadherin
#16
Nives Pećina-Šlaus, Anja Kafka, Tomislav Vladušić, Hrvoje Ivan Pećina, Reno Hrašćan
BACKGROUND/AIM: Tumor suppressor gene AXIN1 is an inhibitor of Wnt signaling pathway. It down-regulates the pathway's main signaling effector molecule, beta-catenin, in an AXIN-based destruction complex. In the present study we investigated the involvement of AXIN1 in intracranial meningioma. MATERIALS AND METHODS: Loss of heterozygosity and microsatellite instability analyses were performed. The consequences of genetic changes on protein expression levels were studied in the same patients by immunohistochemistry...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27611941/nts-ntr1-co-expression-enhances-epithelial-to-mesenchymal-transition-and-promotes-tumor-metastasis-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway-in-hepatocellular-carcinoma
#17
Yingnan Ye, Xinxin Long, Lijie Zhang, Jieying Chen, Pengpeng Liu, Hui Li, Feng Wei, Wenwen Yu, Xiubao Ren, Jinpu Yu
Neurotensin (NTS) is a neuropeptide distributed in central nervous and digestive systems. In this study, the significant association between ectopic NTS expression and tumor invasion was confirmed in hepatocellular carcinoma (HCC). In primary HCC tissues, the NTS and neurotensin receptor 1 (NTR1) co-expression (NTS+NTR1+) is a poor prognostic factor correlated with aggressive biological behaviors and poor clinical prognosis. Enhanced epithelial-to-mesenchymal transition (EMT) features, including decreased E-cadherin, increased β-catenin translocation and N-cadherin expression, were identified in NTS+NTR1+ HCC tissues...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27596264/kif3a-binds-to-%C3%AE-arrestin-for-suppressing-wnt-%C3%AE-catenin-signalling-independently-of-primary-cilia-in-lung-cancer
#18
Minsuh Kim, Young-Ah Suh, Ju-Hee Oh, Bo Ra Lee, Joon Kim, Se Jin Jang
Aberrant Wnt/β-catenin signalling is implicated in the progression of several human cancers, including non-small cell lung cancer (NSCLC). However, mutations in Wnt/β-catenin pathway components are uncommon in NSCLC, and their epigenetic control remains unclear. Here, we show that KIF3A, a member of the kinesin-2 family, plays a role in suppressing Wnt/β-catenin signalling in NSCLC cells. KIF3A knockdown increases both β-catenin levels and transcriptional activity with concomitant promotion of malignant potential, such as increased proliferation and migration and upregulation of stemness markers...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27577083/prognostic-impact-of-the-expression-of-wnt-signaling-proteins-in-cervical-carcinoma-figo-stage-i-iv-treated-with-radiotherapy-or-chemoradiotherapy
#19
Louise Bohr Mordhorst, Cecilia Ahlin, Bengt Sorbe
Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively...
27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27521891/dixdc1-targets-cyclind1-and-p21-via-pi3k-pathway-activation-to-promote-schwann-cell-proliferation-after-sciatic-nerve-crush
#20
Weijie Wu, Qingqing Liu, Yuxi Liu, Zhaohui Yu, Youhua Wang
Dixdc1 (DIX domain containing-1), the mammalian homolog of Ccd1 (Coiled-coil-Dishevelled-Axin1), is a protein containing a coiled-coil domain and a Dishevelled-Axin (DIX) domain. As a novel component of the Wnt pathway, Dixdc1 has been reported to be able to promote neural progenitor proliferation and neuronal differentiation via Wnt/β-catenin signaling. But there still remains something unknown about Dixdc1 distribution and functions in the lesion and regeneration of the peripheral nervous system (PNS), so we tried to investigate dynamic changes of Dixdc1 expression in a rat sciatic nerve crush (SNC) model in this study...
September 16, 2016: Biochemical and Biophysical Research Communications
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