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https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#1
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27908243/mitochondria-targeted-antioxidant-skqr1-reduces-tnf-induced-endothelial-permeability-in-vitro
#2
I I Galkin, O Yu Pletjushkina, R A Zinovkin, V V Zakharova, B V Chernyak, E N Popova
Prolonged or excessive increase in the circulatory level of proinflammatory tumor necrosis factor (TNF) leads to abnormal activation and subsequent damage to endothelium. TNF at high concentrations causes apoptosis of endothelial cells. Previously, using mitochondria-targeted antioxidants of SkQ family, we have shown that apoptosis of endothelial cells is dependent on the production of reactive oxygen species (ROS) in mitochondria (mito-ROS). Now we have found that TNF at low concentrations does not cause cell death but activates caspase-3 and caspase-dependent increase in endothelial permeability in vitro...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27903708/astrocyte-elevated-gene-1-regulates-beta-catenin-signaling-to-maintain-glioma-stem-like-stemness-and-self-renewal
#3
Bin Hu, Luni Emdad, Timothy P Kegelman, Xue-Ning Shen, Swadesh K Das, Devanand Sarkar, Paul B Fisher
: Glioblastoma multiforme (GBM) is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSCs) are responsible for GBM escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers including GBM, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology...
November 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#4
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895723/cisplatin-induced-regulation-of-signal-transduction-pathways-and-transcription-factors-in-p53-mutated-subclone-variants-of-hepatoma-cells-potential-application-for-therapeutic-targeting
#5
Jinn-Rung Kuo, Hung-Sheng Shang, Chun-Te Ho, Kun-Goung Lai, Tsan-Zon Liu, Yin-Ju Chen, Jeng-Fong Chiou
Cisplatin is commonly recognized as a DNA-damaging drug; however, its versatile antitumor effects have been demonstrated to extend beyond this narrow functional attribute. The present study determined how cisplatin regulates alternative pathways and transcription factors to exert its additional antitumor actions. Cisplatin was observed to be able to trigger an endoplasmic reticulum stress response through aggravated nitrosative stress coupled to perturbed mitochondrial calcium (Ca(2+)) homeostasis, which substantially downregulated glucose-regulated protein (GRP) 78 expression by suppressing the cleavage of activating transcription factor (ATF) 6α (90 kDa) to its active 50 kDa subunit...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27883247/2-methoxyestradiol-mediated-induction-of-frzb-contributes-to-cell-death-and-autophagy-in-mg63-osteosarcoma-cells
#6
Dalibel Bravo, Kristen L Shogren, Dongqing Zuo, Eric R Wagner, Gobinda Sarkar, Michael J Yaszemski, Avudaiappan Maran
Osteosarcoma is a bone tumor that mainly affects children and adolescents. Although its pathogenesis is still not fully understood, activation of Wnt signaling has been implicated in the development and metastasis of osteosarcoma. In this report, we have investigated the effect of the anti-tumor compound, 2-methoxyestradiol (2-ME) on Wnt antagonist frizzled-related protein b (Frzb), also known as secreted frizzled-related protein (sFRP)3 in human osteosarcoma (MG63) cells. Our results show that 2-ME treatment induces Frzb gene promoter activity, and increases Frzb mRNA and protein levels in osteosarcoma cells...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27878257/downregulation-of-bmi-1-suppresses-epithelial%C3%A2-mesenchymal-transition-in-melanoma
#7
Yanting Liu, Zhaowei Chu, Qingyan Li, Bin Peng, Suyun Xu, Christine G Lian, Songmei Geng
Epithelial-mesenchymal transition (EMT) contributes to the invasion and metastasis of numerous malignant cancers, including melanoma. A significant higher expression of B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) has been reported in cell lines from metastatic melanoma compared to cell lines from primary melanoma. There are studies that show that knockdown of Bmi-1 could induce E-cadherin expression in melanoma cells. However, the role of Bmi-1 in mediating EMT-like changes in melanoma has not yet been fully studied...
November 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27872325/the-molecular-circuit-regulating-tooth-development-in-crocodilians
#8
S Tsai, A Abdelhamid, M K Khan, A Elkarargy, R B Widelitz, C M Chuong, P Wu
Alligators have robust regenerative potential for tooth renewal. In contrast, extant mammals can either renew their teeth once (diphyodont dentition, as found in humans) or not at all (monophyodont dentition, present in mice). Previously, the authors used multiple mitotic labeling to map putative stem cells in alligator dental laminae, which contain quiescent odontogenic progenitors. The authors demonstrated that alligator tooth cycle initiation is related to β-catenin/Wnt pathway activity in the dental lamina bulge...
December 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27871853/nur77-downregulation-triggers-pulmonary-artery-smooth-muscle-cell-proliferation-and-migration-in-mice-with-hypoxic-pulmonary-hypertension-via-the-axin2-%C3%AE-catenin-signaling-pathway
#9
Xiaowei Nie, Jianxin Tan, Youai Dai, Wenjun Mao, Yuan Chen, Guowei Qin, Guirong Li, Chenyou Shen, Jingjing Zhao, Jingyu Chen
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases...
November 15, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27870635/alternative-exon-usage-creates-novel-transcript-variants-of-tumor-suppressor-shrew-1-gene-with-differential-tissue-expression-profile
#10
Petra A B Klemmt, Eduard Resch, Isabell Smyrek, Knut Engels, Ernst H K Stelzer, Anna Starzinski-Powitz
Shrew-1, also called AJAP1, is a transmembrane protein associated with E-cadherin-mediated adherence junctions and a putative tumor suppressor. Apart from its interaction with β-catenin and involvement in E-cadherin internalization, little structure or function information exists. Here we explored shrew-1 expression during postnatal differentiation of mammary gland as a model system. Immunohistological analyses with antibodies against either the extracellular or the cytoplasmic domains of shrew-1 consistently revealed the expression of full-length shrew-1 in myoepithelial cells, but only part of it in luminal cells...
November 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27836546/apbb1-reinforces-cancer-stem-cell-and-epithelial-to-mesenchymal-transition-by-regulating-the-igf1r-signaling-pathway-in-non-small-cell-lung-cancer-cells
#11
Jei Ha Lee, Jung Yul Kim, Seo Yeon Kim, Soo Im Choi, Kuk Chan Kim, Eun Wie Cho, In Gyu Kim
Amyloid β precursor protein binding family B member 1(APBB1) was first identified as a binding partner of amyloid precursor protein during brain development, but its function in the context of cancer remain unclear. Here we show for the first time that APBB1 is partly associated with intensifying cancer stem cell(CSC) and epithelial-to-mesenchymal transition (EMT) and enhancing radiation-resistant properties of lung cancer cells. We found that APBB1 was highly expressed in ALDH1(high) CSC-like cells sorted from A549 lung cancer cells...
November 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27835587/nerve-growth-factor-modulates-the-tumor-cells-migration-in-ovarian-cancer-through-the-wnt-%C3%AE-catenin-pathway
#12
Bo Li, Shaoxi Cai, Yi Zhao, Qiyi He, Xiaodong Yu, Longcong Cheng, Yingfeng Zhang, Xiancheng Hu, Ming Ke, Sijia Chen, Misha Zou
Nerve growth factor (NGF)/nerve growth factor receptors (NGFRs) axis and canonical WNT/β-catenin pathway have shown to play crucial roles in tumor initiation, progression and prognosis. But little did we know the relationship between them in modulation of tumor progress. In this report, we found that NGF/NGFRs and β-catenin were coexpression in ovarian cancer cell lines, and NGF can decrease the expression level of β-catenin and affect its activities, which may be related to the NGF-induced down-regulation of B-cell CLL/lymphoma 9-like (BCL9L, BCL9-2)...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831561/rapidly-cycling-lgr5-stem-cells-are-exquisitely-sensitive-to-extrinsic-dietary-factors-that-modulate-colon-cancer-risk
#13
Eunjoo Kim, Laurie A Davidson, Roger S Zoh, Martha E Hensel, Michael L Salinas, Bhimanagouda S Patil, Guddadarangavvanahally K Jayaprakasha, Evelyn S Callaway, Clinton D Allred, Nancy D Turner, Brad R Weeks, Robert S Chapkin
The majority of colon tumors are driven by aberrant Wnt signaling in intestinal stem cells, which mediates an efficient route toward initiating intestinal cancer. Natural lipophilic polyphenols and long-chain polyunsaturated fatty acids (PUFAs) generally suppress Wnt- and NF-κB- (nuclear factor-κ light-chain enhancer of activated B-cell) related pathways. However, the effects of these extrinsic agents on colonic leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5(+)) stem cells, the cells of origin of colon cancer, have not been documented to date...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27819675/induction-of-endoplasmic-reticulum-stress-by-deletion-of-grp78-depletes-apc-mutant-intestinal-epithelial-stem-cells
#14
J F van Lidth de Jeude, B J Meijer, M C B Wielenga, C N Spaan, B Baan, S L Rosekrans, S Meisner, Y H Shen, A S Lee, J C Paton, A W Paton, V Muncan, G R van den Brink, J Heijmans
Intestinal epithelial stem cells are highly sensitive to differentiation induced by endoplasmic reticulum (ER) stress. Colorectal cancer develops from mutated intestinal epithelial stem cells. The most frequent initiating mutation occurs in Apc, which results in hyperactivated Wnt signalling. This causes hyperproliferation and reduced sensitivity to chemotherapy, but whether these mutated stem cells are sensitive to ER stress induced differentiation remains unknown. Here we examined this by generating mice in which both Apc and ER stress repressor chaperone Grp78 can be conditionally deleted from the intestinal epithelium...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27811361/the-role-of-pygo2-for-wnt-%C3%A3-catenin-signaling-activity-during-intestinal-tumor-initiation-and-progression
#15
Suranand B Talla, Felix H Brembeck
Pygo2 acts as a co-activator of Wnt signaling in a nuclear complex with ß-catenin/BCL9/BCL9-2 to increase target gene transcription. Previous studies showed that Pygo2 is upregulated in murine intestinal tumors and human colon cancer, but is apparently dispensable for normal intestinal homeostasis. Here, we have evaluated the in vivo role of Pygo2 during intestinal tumorigenesis using Pygo2 deficient mice. We analyzed chemically induced colon tumor development and conditional intestine specific mouse models harboring either Apc loss-of-function (LOF) or Ctnnb1 gain-of-function (ß-catenin GOF)...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27806760/-the-crosstalk-between-canonical-and-noncanonical-wnt-signaling-pathway-in-osteoblast-differentiation-of-periodontal-ligament-stem-cells-in-inflammatory-microenvironments
#16
N Liu, H G Shi, W Zhang, B Gu
Objective: To investigate the crosstalk between canonical Wnt/β-catenin and noncanonical Wnt/Ca(2+) pathway in osteoblast differentiation process of periodontal ligament stem cell (PDLSC) in inflammatory microenvironments. Methods: PDLSCs were obtained from human healthy individuals(H-PDLSC) and patients with periodontitis(P-PDLSC). The H/P-PDLSCs were transfected with β-catenin siRNA. Cell morphology was observed under fluorescent microscope and transfection efficiency was easured by Western blotting after transfection of PDLSC...
November 9, 2016: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
https://www.readbyqxmd.com/read/27801341/-the-expression-of-p27-kip1-and-%C3%AE-catenin-in-multiple-endocrine-neoplasia-type-1-related-parathyroid-tumors
#17
J Kong, O Wang, M Nie, J Shi, Y Jiang, M Li, W B Xia, X W Meng, X P Xing
Objective: To explore tissue expression of cyclin-dependent kinase inhibitor p27(Kip1) and β-catenin in multiple endocrine neoplasia type1 (MEN1)-related parathyroid tumors (MHPT). Methods: Immunohistochemistry was performed to analyze the expression of p27(Kip1) and β-catenin in parathyroid glands from 31 subjects with MHPT collected at Peking Union Medical College Hospital from 2002 to 2013. Five normal parathyroid glands were used as control. Results: In MHPT subjects, nuclear expression of p27(Kip1) was absent in 4 (12...
November 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/27798885/%C3%AE-catenin-expression-regulates-cell-migration-of-human-colonic-adenocarcinoma-cells-through-gelsolin
#18
Dagmara Baczynska, Izabela Bombik, Maria Malicka-Błaszkiewicz
BACKGROUND/AIM: β-Catenin is one of the key players in colonic carcinogenesis. Being part of the E-cadherin complex, it regulates cell-cell adhesion and the migratory ability of cells. However, the role of nuclear β-catenin in the cell migration process is poorly understood. Gelsolin is one of the most abundant actin-binding proteins, and is implicated in tumour cell motility and invasiveness. The aim of the present study was to evaluate the potential association between expression of β-catenin and gelsolin, and their influence on the migration ability of colon adenocarcinoma LS180 cells...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27793889/targeting-cellular-signaling-pathways-in-breast-cancer-stem-cells-and-its-implication-for-cancer-treatment
#19
REVIEW
Bruno Ricardo Barreto Pires, Ísis Salviano Soares DE Amorim, Layane Duarte E Souza, Juliana Alves Rodrigues, Andre Luiz Mencalha
Breast cancer is a public health problem both in developing and developed countries. The breast cancer stem cell (BCSC) hypothesis has grown in the cancer research community. These BCSCs comprise of a small subpopulation of cells within the tumor mass which exhibit stem cell-like characteristics and have emerged as being responsible for tumor development, recurrence and metastasis in BC. The complexity of control of gene expression in BCSC is commonly driven by a myriad of signaling pathways triggered by extracellular signals, mutations and epigenetic control...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27793772/tcf7l2-mediates-the-cellular-and-behavioral-response-to-chronic-lithium-treatment-in-animal-models
#20
Katarzyna Misztal, Nikola Brozko, Andrzej Nagalski, Lukasz M Szewczyk, Marta Krolak, Katarzyna Brzozowska, Jacek Kuznicki, Marta B Wisniewska
The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus...
October 25, 2016: Neuropharmacology
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