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Chen-Xu Ni, Yang Qi, Jin Zhang, Ying Liu, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Qiu-Ye Wu, Yan Wang, Jun-Ping Zhang
The eradication of cancer stem cells (CSCs) is significant for cancer therapy and prevention. In this study, we evaluated WM130, a novel derivative of matrine, for its effect on CSCs using human hepatocellular carcinoma (HCC) cell lines, their sphere cells, and sorted EpCAM+ cells. We revealed that WM130 could not only inhibit proliferation and colony formation of HCC cells, but also suppress the expression of some stemness-related genes and up-regulate some mature hepatocyte marker genes, indicating a promotion of differentiation from CSCs to hepatocytes...
October 22, 2016: Oncotarget
Bo Yang, Shiming Zhang, Zhihao Wang, Chunxu Yang, Wen Ouyang, Fuxiang Zhou, Yunfeng Zhou, Conghua Xie
β-catenin is a crucial signal transduction molecule in the Wnt/β-catenin signal pathway, and increased β-catenin expression has consistently been found in high grade gliomas. However, the mechanisms responsible for β-catenin overexpression have remained elusive. Here we show that the deubiquitinase USP9X stabilizes β-catenin and thereby promotes high grade glioma cell growth. USP9X binds β-catenin and removes the Lys 48-linked polyubiquitin chains that normally mark β-catenin for proteasomal degradation...
October 22, 2016: Oncotarget
Yi-Cun Li, Lin-Lin Bu, Liang Mao, Si-Rui Ma, Jian-Feng Liu, Guang-Tao Yu, Wei-Wei Deng, Wen-Feng Zhang, Zhi-Jun Sun
OBJECTIVE: Our aim is to evaluate the expression of SATB1 in human oral squamous cell carcinomas (OSCC) and its role in the invasiveness and metastasis of OSCC. SUBJECTS AND METHODS: A human OSCC tissue microarray was used to evaluate the expression pattern of SATB1. SATB1 mRNA knockdown was performed in human OSCC cell lines SCC25 and Cal27 to assess the function of SATB1 in the invasiveness and metastasis of OSCC. RESULTS: SATB1 is highly expressed in human OSCC determined by immunohistochemistry and its nuclear/cytoplasmic ratio of histoscore is significantly correlated with patients' prognosis...
October 26, 2016: Oral Diseases
Blair W Benham-Pyle, Joo Yong Sim, Kevin C Hart, Beth L Pruitt, William James Nelson
Mechanical force and Wnt signaling activate β-catenin-mediated transcription to promote proliferation and tissue expansion. However, it is unknown whether mechanical force and Wnt signaling act independently or synergize to activate β-catenin signaling and cell division. We show that mechanical strain induced Src-dependent phosphorylation of Y654 β-catenin and increased β-catenin-mediated transcription in mammalian MDCK epithelial cells. Under these conditions, cells accumulated in S/G2 (independent of DNA damage) but did not divide...
October 26, 2016: ELife
Irene D Román, David Cano-Martínez, María Val T Lobo, María Dolores Fernández-Moreno, Borja Hernández-Breijo, Silvia Sacristán, Patricia Sanmartín-Salinas, Jorge Monserrat, Javier P Gisbert, Luis G Guijarro
: Objetive: Our purpose was to study the molecular basis of infliximab (IFX) effect on colon mucosa in a colitis model and to identify new biomarkers of mucosal healing. METHODS: Healthy rats and rats which were subjected to experimental colitis induced by dextran sulphate sodium, with or without IFX treatment (in the short- and long-term), were studied along with forty-seven IBD patients. Colon mucosal integrity by Periodic Acid Schiff staining, intestinal damage by immunohistochemistry (proliferating cell nuclear antigen, β-catenin, E-cadherin, phosphotyrosine, p-p38, allograft inflammatory factor-1 (AIF-1) and colonic mucosal apoptosis by TUNEL staining were evaluated in rats...
October 26, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Torsten Pietsch, Christine Haberler
The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma...
October 26, 2016: Clinical Neuropathology
Shingo Shimozaki, Norio Yamamoto, Takahiro Domoto, Hideji Nishida, Katsuhiro Hayashi, Hiroaki Kimura, Akihiko Takeuchi, Shinji Miwa, Kentaro Igarashi, Takashi Kato, Yu Aoki, Takashi Higuchi, Mayumi Hirose, Robert M Hoffman, Toshinari Minamoto, Hiroyuki Tsuchiya
Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3β (GSK- 3β) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3β inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3β in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3β inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice...
October 20, 2016: Oncotarget
Tiansheng Shen, Kui Zhang, Gene P Siegal, Shi Wei
OBJECTIVES: To analyze the expression of E-cadherin and β-catenin in triple-negative breast cancer (TNBC) to assess their prognostic significance. METHODS: The expression of E-cadherin and β-catenin was examined semiquantitatively and correlated with other pathologic factors and survival outcomes. RESULTS: Of 72 consecutive TNBCs, 56% showed reduced membranous expression of E-cadherin or β-catenin, with a strong correlation to each other...
October 25, 2016: American Journal of Clinical Pathology
S Oliveira, A K Samba, A J Towbin, A Gupta, J I Geller, J D Nathan, R Kohli
: Hepatocellular adenomas (HCA) are benign tumours with potential for malignant transformation with no recommendations regarding management in the paediatric population. We report a case of an inflammatory adenoma with β-catenin activated pathway in an obese, paediatric patient with nonalcoholic steatohepatitis (NASH). CASE REPORT: An 11-year-old female presented with a microlobulated liver lesion measuring >5 cm in magnetic resonance imaging (MRI) with inflammatory adenoma with β-catenin activated pathology arising in a background of NASH, nonalcoholic fatty liver disease (NAFLD) activity score 5/8...
October 25, 2016: Pediatric Obesity
Kaichun Li, Mingzhen Ying, Dan Feng, Jie Du, Shiyu Chen, Bing Dan, Cuihua Wang, Yajie Wang
Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is a tumor suppressor that frequently down-regulated in cancers, especially breast cancer. Here, we provide both supporting and contradicting evidences about the expression pattern and function of FBP1 in breast cancer. Data mining of Oncomine database showed that FBP1 is commonly up-regulated in tumor tissues compared with non-tumor tissues regardless of histological type. Analysis of a large-scale cohort derived from Kaplan-Meier Plotter showed that lower FBP1 expression associated with poor clinical outcome...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ye Liu, Di Huang, Zhaoyang Wang, Chao Wu, Zhao Zhang, Dan Wang, Zongjin Li, Tianhui Zhu, Shuang Yang, Wei Sun
The proto-oncogene LIM-domain only 2 (lmo2) was traditionally considered to be a pivotal transcriptional regulator in hematopoiesis and leukemia. Recently, the cytosolic localization of LMO2 was revealed in multiple epithelial tissues and a variety of solid tumors. However, the function of LMO2 in these epithelia and solid tumors remains largely unclear. The Wnt signaling pathway is a crucial determinant of development, and abnormalities in several key segments of this pathway contribute to oncogenesis. The current study demonstrated that LMO2 participates in the regulation of canonical Wnt signaling in the cytoplasm by binding to Dishevelled-1/2 (DVL-1/2) proteins...
October 25, 2016: Scientific Reports
Cheril Tapia-Rojas, Patricia V Burgos, Nibaldo C Inestrosa
Alzheimer's disease (AD) is the most common neurodegenerative disorder and the most frequent cause of dementia in the aged population. According to the amyloid hypothesis, the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of AD. Aβ is generated from the amyloidogenic processing of amyloid precursor protein (APP) and can aggregate to form oligomers, which have been described as a major synaptotoxic agent in neurons. Dysfunction of Wnt signaling has been linked to increased Aβ formation; however, several other studies have argued against this possibility...
October 25, 2016: Journal of Neurochemistry
Bo Shuai, Rui Zhu, Yan-Ping Yang, Lin Shen, Xiao-Juan Xu, Chen Ma, Lin Lu
OBJECTIVE: To investigate the impact of Qing'e Pill (, QEP) on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis. METHODS: Ninety-six 8-week-old specifific pathogen free C57BL/6 mice were randomly divided into 4 groups (24/group): sham, ovariectomised osteoporosis model, oestradiol-treated, and QEP-treated groups. Three months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional (3D) parameters of their cancellous bone microstructure...
October 24, 2016: Chinese Journal of Integrative Medicine
Vassilios Atsaves, Maria G Detsika, Elpida Poulaki, Hara Gakiopoulou, Elias A Lianos
Although the protective role of HO-1 induction in various forms of kidney disease is well established, mechanisms other than heme catabolism to biliverdin, bilirubin and carbon monoxide have recently been identified. Unraveling these mechanisms requires the generation of appropriate animal models. The present study describes the generation of a HO-1 deficient Hmox1 (-/-) rat model and characterizes its renal and extrarenal phenotype. Hmox1 (-/-) rats had growth retardation and splenomegaly compared to their Hmox1 (+/+) littermates...
October 24, 2016: Transgenic Research
Pomila Singh, Malaney O'Connell, Sarkar Shubhashish
Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation...
2016: Stem Cell Investigation
Brie Sorrenson, Emmanuelle Cognard, Kathryn L Lee, Waruni C Dissanayake, Yanyun Fu, Weiping Han, William E Hughes, Peter R Shepherd
The processes regulating glucose-stimulated insulin secretion (GSIS) and its modulation by incretins in pancreatic β-cells are only partly understood. Here we investigate the involvement of β-catenin in these processes. Reducing β-catenin levels using siRNA knockdown attenuated GSIS in a range of β-cell models and blocked the ability of GLP-1 agonists and the depolarizing agent KCl to potentiate this. This could be mimicked in both β-cell models and isolated islets by short-term exposure to the β-catenin inhibitory drug pyrvinium...
October 24, 2016: Journal of Biological Chemistry
Srikanth R Polusani, Edward A Kalmykov, Anjana Chandrasekhar, Shoshanna N Zucker, Bruce J Nicholson
Gap junction proteins (connexins) have critical effects on cell motility in many systems, from migration of neural crest cells to promotion of metastatic invasiveness, Here we show that expression of Cx26 in HeLa cells specifically enhances cell motility in scrape wounding and sparse culture models. This effect is dependent on gap junction channels and is isotype specific (Cx26 enhances motility, while Cx43 does not. Cx32 has an intermediate effect). The increased motility is associated with reduced cell adhesiveness, caused by loss of N-cadherin protein and RNA at the wound edge...
October 24, 2016: Journal of Cell Science
Giulia Ramazzotti, Irene Faenza, Roberta Fiume, Anna Maria Billi, Lucia Manzoli, Sara Mongiorgi, Stefano Ratti, James A McCubrey, Pann-Ghill Suh, Lucio Cocco, Matilde Y Follo
Phosphoinositide-phospholipase C-β1 (PLC-β1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation and osteogenesis. During myogenic differentiation of murine C2C12 myoblasts, PLC-β1 signaling pathway involves the Inositol Polyphosphate Multikinase (IPMK) and β-catenin as downstream effectors. By means of c-jun binding to cyclin D3 promoter, the activation of PLC-β1 pathway determines cyclin D3 accumulation. However, osteogenesis requires PLC-β1 expression and up-regulation but it does not affect cyclin D3 levels, suggesting that the two processes require the activation of different mediators...
October 18, 2016: Advances in Biological Regulation
Yuanfei Zhou, Tingxing Song, Jie Peng, Zheng Zhou, Hongkui Wei, Rui Zhou, Siwen Jiang, Jian Peng
Sirtuin 1 (SIRT1) regulates adipocyte and osteoblast differentiation. However, the underlying mechanism should be investigated. This study revealed that SIRT1 acts as a crucial repressor of adipogenesis. RNA-interference-mediated SIRT1 knockdown or genetic ablation enhances adipogenic potential, whereas SIRT1 overexpression inhibits adipogenesis in mesenchymal stem cells (MSCs). SIRT1 also deacetylates the histones of sFRP1, sFRP2, and Dact1 promoters; inhibits the mRNA expression of sFRP1, sFRP2, and Dact1; activates Wnt signaling pathways; and suppresses adipogenesis...
October 20, 2016: Oncotarget
Mijung Kwon, Jae-Hoon Kim, Yevangelina Rybak, Alex Luna, Chel Hun Choi, Joon-Yong Chung, Stephen M Hewitt, Asha Adem, Elizabeth Tubridy, Juan Lin, Steven K Libutti
Filamin A interacting protein 1-like (FILIP1L) is an inhibitor of the canonical WNT pathway. WNT/β-catenin signaling and its downstream pathway, epithelial-to-mesenchymal transition (EMT), play a key role in ovarian cancer metastasis and chemoresistance. To study the clinical implications of FILIP1L in regulating the WNT/β-catenin pathway, the expression of FILIP1L, β-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic...
October 20, 2016: Oncotarget
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