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https://www.readbyqxmd.com/read/28103576/a-new-model-of-multi-visceral-and-bone-metastatic-prostate-cancer-with-perivascular-niche-targeting-by-a-novel-endothelial-specific-adenoviral-vector
#1
Zhi Hong Lu, Sergey Kaliberov, Rebecca E Sohn, Lyudmila Kaliberova, Yingqiu Du, Julie L Prior, Daniel J Leib, Anne Chauchereau, Jennifer K Sehn, David T Curiel, Jeffrey M Arbeit
While modern therapies for metastatic prostate cancer (PCa) have improved survival they are associated with an increasingly prevalent entity, aggressive variant PCa (AVPCa), lacking androgen receptor (AR) expression, enriched for cancer stem cells (CSCs), and evidencing epithelial-mesenchymal plasticity with a varying extent of neuroendocrine transdifferentiation. Parallel work revealed that endothelial cells (ECs) create a perivascular CSC niche mediated by juxtacrine and membrane tethered signaling. There is increasing interest in pharmacological metastatic niche targeting, however, targeted access has been impossible...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103279/aristaless-related-homeobox-arx-interacts-with-%C3%AE-catenin-bcl9-and-p300-to-regulate-canonical-wnt-signaling
#2
Il-Taeg Cho, Youngshin Lim, Jeffrey A Golden, Ginam Cho
Mutations in the Aristaless Related Homeobox (ARX) gene are associated with a spectrum of structural (lissencephaly) and functional (epilepsy and intellectual disabilities) neurodevelopmental disorders. How mutations in this single transcription factor can result in such a broad range of phenotypes remains poorly understood. We hypothesized that ARX functions through distinct interactions with specific transcription factors/cofactors to regulate unique target genes in different cell types. To identify ARX interacting proteins, we performed an unbiased proteomics screen and identified several components of the Wnt/β-catenin signaling pathway, including β-catenin (CTNNB1), B-cell CLL/lymphoma 9 (BCL9) and leucine rich repeat flightless interacting protein 2 (LRRFIP2), in cortical progenitor cells...
2017: PloS One
https://www.readbyqxmd.com/read/28102847/curcumin-represses-mouse-3t3-l1-cell-adipogenic-differentiation-via-inhibiting-mir-17-5p-and-stimulating-the-wnt-signalling-pathway-effector-tcf7l2
#3
Lili Tian, Zhuolun Song, Weijuan Shao, William W Du, Lisa R Zhao, Kejing Zeng, Burton B Yang, Tianru Jin
Understanding mechanisms underlying adipogenic differentiation may lead to the discovery of novel therapeutic targets for obesity. Wnt signalling pathway activation leads to repressed adipogenic differentiation while certain microRNAs may regulate pre-adipocyte proliferation and differentiation. We show here that in mouse white adipose tissue, miR-17-5p level is elevated after high fat diet consumption. miR-17-5p upregulates adipogenic differentiation, as its over-expression increased while its inhibition repressed 3T3-L1 differentiation...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102846/hepatitis-b-virus-x-protein-promotes-the-stem-like-properties-of-ov6-cancer-cells-in-hepatocellular-carcinoma
#4
Chao Wang, Ming-da Wang, Peng Cheng, Hai Huang, Wei Dong, Wei-Wei Zhang, Peng-Peng Li, Chuan Lin, Ze-Ya Pan, Meng-Chao Wu, Wei-Ping Zhou
Hepatitis B virus X protein (HBx) and cancer stem-like cells (CSCs) have both been implicated in the occurrence and development of HBV-related hepatocellular carcinoma (HCC). However, whether HBx contributes to the stem-like properties of OV6(+) CSCs in HCC remains elusive. In this study, we showed that the concomitant expression of HBx and OV6 was closely associated with the clinical outcomes and prognosis of patients with HBV-related HCC. HBx was required for the stem-like properties of OV6(+) liver CSCs, including self-renewal, stem cell-associated gene expression, tumorigenicity and chemoresistance...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102559/effect-of-bone-like-hydroxyapatite-poly-amino-acid-loaded-with-rifapentine-microspheres-on-bone-and-joint-tuberculosis-in-vitro
#5
Yuwu Liu, Dianming Jiang
Rifapentine-loaded poly(lactic-co-glycolic acid) microspheres (RPMs)-loaded bone-like hydroxyapatite/poly amino acid (BHA/PAA) is effective in curing S. aureus-induced chronic osteomyelitis. This study continues to investigate the effect of RPM-loaded BHA/PAA on the bacterial growth of Mycobacterium tuberculosis (MTB), cell proliferation and differentiation in MTB H37Rv-infected MG63 cells. Furthermore, whether Wnt/β-catenin signaling pathway was activated by RPM-loaded BHA/PAA was explored. We found the bactec growth index of H37Rv was significantly inhibited by RPM-loaded BHA/PAA...
January 19, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28102204/the-prevalence-of-ctnnb1-mutations-in-primary-aldosteronism-and-consequences-for-clinical-outcomes
#6
Vin-Cent Wu, Shuo-Meng Wang, Shih-Chieh Jeff Chueh, Shao-Yu Yang, Kuo-How Huang, Yen-Hung Lin, Jian-Jhong Wang, Rory Connolly, Ya-Hui Hu, Celso E Gomez-Sanchez, Kang-Yung Peng, Kwan-Dun Wu
Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101909/efficient-transdifferentiation-of-human-dermal-fibroblasts-into-skeletal-muscle
#7
Selwa Mokhtar Boularaoui, Khaled M A Abdel-Raouf, Noaf Salah Ali Alwahab, Megan E Kondash, George A Truskey, Jeremy Choon Meng Teo, Nicolas Christoforou
Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused due to severe injury, congenital defects, or tumor ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28101190/ror2-inhibits-the-proliferation-of-gastric-carcinoma-cells-via-activation-of-non-canonical-wnt-signaling
#8
Likun Yan, Qingguo Du, Jianfeng Yao, Ruiting Liu
Gastric carcinoma is one of the most common human cancers and has a poor prognosis. Receptor tyrosine kinase-like orphan receptor 2 (ROR2), which is a non-canonical receptor of the Wnt signaling pathway, has been reported to be deregulated in numerous types of human cancers, including gastric carcinoma. However, the exact role of ROR2 in the regulation of the malignant phenotypes of gastric carcinoma, as well as the underlying molecular mechanism, remains largely unclear. The present study demonstrated that ROR2 was recurrently downregulated in gastric carcinoma tissues, as compared with their matched adjacent normal tissues...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28101169/role-of-wnt-%C3%AE-catenin-wnt-c-jun-n-terminal-kinase-and-wnt-ca-2-pathways-in-cisplatin-induced-chemoresistance-in-ovarian-cancer
#9
Lu Huang, Ye Jin, Shujun Feng, Yuqing Zou, Sainan Xu, Shuang Qiu, Ling Li, Jianhua Zheng
The aim of the present study was to explore the expression of Wnt signaling proteins β-catenin, c-Jun N-terminal kinase (JNK) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in ovarian cancer cells, and assess the correlation between this expression and cisplatin-induced chemoresistance. SKOV3 ovarian carcinoma cells and SKOV3/DDP (cisplatin resistant) cells were treated with cisplatin in the absence or presence of a Wnt signaling activator (CHIR-99021, glycogen synthase kinase 3β inhibitor) or inhibitor (XAV-939, tankyrase inhibitor)...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100780/a-novel-microrna-located-in-trkc-gene-regulates-wnt-signaling-pathway-and-is-differentially-expressed-in-colorectal-cancer-specimens
#10
Sadat Dokanehiifard, Atena Yasari, Hadi Najafi, Meisam Jafarzadeh, Maryam Nikkhah, Seyed Javad Mowla, Bahram M Soltani
Tropomyosin receptor kinase C (TrkC) is involved in cell survival, apoptosis, differentiation and tumorigenesis. TrkC diverse functions might be attributed to the hypothetical non-coding RNAs, embedded within the gene. Using bioinformatics approaches, a novel miRNA named TrkC-miR2 was predicted within TrkC gene, capable of regulating Wnt pathway. For experimental verification of this miRNA, predicted TrkC-premir2 sequence was overexpressed in SW480 cells, which led to the detection of two mature TrkC-miR2 isomiRs, and their endogenous forms were detected in human cell lines as well...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100625/the-ptpn14-tumour-suppressor-is-a-degradation-target-of-human-papillomavirus-e7
#11
Anita Szalmás, Vjekoslav Tomaić, Om Basukala, Paola Massimi, Suruchi Mittal, József Kónya, Lawrence Banks
: Activation of signalling pathways ensuring cell growth are essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumour suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signalling pathways. In this study we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100566/loss-of-axin1-drives-acquired-resistance-to-wnt-pathway-blockade-in-colorectal-cancer-cells-carrying-rspo3-fusions
#12
Gabriele Picco, Consalvo Petti, Alessia Centonze, Erica Torchiaro, Giovanni Crisafulli, Luca Novara, Andrea Acquaviva, Alberto Bardelli, Enzo Medico
In colorectal cancer (CRC), WNT pathway activation by genetic rearrangements of RSPO3 is emerging as a promising target. However, its low prevalence severely limits availability of preclinical models for in-depth characterization. Using a pipeline designed to suppress stroma-derived signal, we find that RSPO3 "outlier" expression in CRC samples highlights translocation and fusion transcript expression. Outlier search in 151 CRC cell lines identified VACO6 and SNU1411 cells as carriers of, respectively, a canonical PTPRK(e1)-RSPO3(e2) fusion and a novel PTPRK(e13)-RSPO3(e2) fusion...
January 18, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28099945/in-vivo-and-in-vitro-effects-of-microrna-27a-on-proliferation-migration-and-invasion-of-breast-cancer-cells-through-targeting-of-sfrp1-gene-via-wnt-%C3%AE-catenin-signaling-pathway
#13
Ling-Yu Kong, Mei Xue, Qing-Cai Zhang, Chuan-Fu Su
This study aims to explore the effects of microRNA-27a (miR-27a) targeting of SFRP1 on the proliferation, migration and invasion of breast cancer (BC) cells through the regulation of Wnt/β-catenin signaling pathway. BC and normal breast tissues were obtained from 396 female BC patients and 308 female patients with benign breast lesions respectively. Human normal mammary epithelial (MCF-10A) and BC cell lines (BT-20, MCF-7, T-47D and MDA-MB-231) were cultured. After cell transfection, BC cells were assigned to six groups: control, miR-27a mimics, miR-27a inhibitors, negative control (NC), si-SFRP1 and si-SFRP1 + miR-27a inhibitors groups...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099467/senescent-atrophic-epidermis-retains-lrig1-stem-cells-and-loses-wnt-signaling-a-phenotype-shared-with-cd44ko-mice
#14
Laurent Barnes, Jean-Hilaire Saurat, Gürkan Kaya
Lrig1 is known to repress the epidermal growth through its inhibitory activity on EGFR, while CD44 promotes it. We analyzed the expression of these molecules in senescent atrophic human epidermis and in the epidermis of CD44KO mice. In normal human epidermis, Lrig1+ cells form clusters located in the basal layer in which CD44 expression is downregulated and Lef1 expression reflects an active Wnt signaling. In senescent atrophic human epidermis, we found retention of Lrig1high+ cells all along the basal layer, forming no clusters, with decrease of CD44 and lef1 expression...
2017: PloS One
https://www.readbyqxmd.com/read/28098905/cripto-1-promotes-epithelial-mesenchymal-transition-in-prostate-cancer-via-wnt-%C3%AE-catenin-signaling
#15
Yan Liu, Zhenbang Qin, Kuo Yang, Ranlu Liu, Yong Xu
The Cripto-1 (CR-1) derived EGF-CFC family was overexpressed in tumor development enhancing proliferation, epithelial-mesenchymal transition (EMT) and migration of tumor cells. However, correlation between CR-1 and prostate cancer (PCa) remains still unclear. In the present study, we proved that CR-1 was expressed in PCa and its function was in the progression of PCa. Compared with benign prostatic hyperplasia (BPH) tissues, we confirmed that PCa tissues had high expression of CR-1 by immunohistochemistry and statistical data showed that CR-1 promoted properties of EMT in PCa tissues, including the downregulation of the cell adhesion molecules β-catenin (membrane) and E-cadherin while upregulating transcription factors β-catenin...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098310/a-computational-model-predicts-genetic-nodes-that-allow-switching-between-species-specific-responses-in-a-conserved-signaling-network
#16
Adriana T Dawes, David Wu, Karley K Mahalak, Edward M Zitnik, Natalia Kravtsova, Haiwei Su, Helen M Chamberlin
Cell signaling networks regulate a variety of developmental and physiological processes, and changes in their response to external stimuli are often implicated in disease initiation and progression. To elucidate how different responses can arise from conserved signaling networks, we have developed a mathematical model of the well-characterized Caenorhabditis vulval development network involving EGF, Wnt and Notch signaling that recapitulates biologically observed behaviors. We experimentally block a specific element of the EGF pathway (MEK), and find different behaviors in vulval development in two Caenorhabditis species, C...
January 18, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28097806/a-silicone-rubber-membrane-with-a-specific-pore-size-enhances-cell-proliferation-and-wound-regeneration-via-the-wnt-%C3%AE-catenin-pathway
#17
Rui Xu, Yang Bai, Jian Zhao, Hesheng Xia, Yi Kong, Zhihui Yao, Rongshuai Yan, Xiaorong Zhang, Xiaohong Hu, Meixi Liu, Qingwu Yang, Gaoxing Luo, Jun Wu
A porous structure is critically important for wound dressing or tissue engineering scaffolds. However, the influence of the pore sizes on cell proliferation, tissue regeneration and the underlying mechanism remains unclear. In this study, silicone rubber membranes with different pore sizes were prepared using certain constituents of liquid silicone rubber (LSR) precursor/ liquid paraffin (LP) /hexane based on our previous studies. It was found that pore size had a significant impact on cell proliferation and wound healing...
January 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097777/activin-a-in-combination-with-erk1-2-mapk-pathway-inhibition-sustains-propagation-of-mouse-embryonic-stem-cells
#18
Yuhei Ashida, May Nakajima-Koyama, Akira Hirota, Takuya Yamamoto, Eisuke Nishida
The Activin/Nodal/TGF-β signaling pathway plays a major role in maintaining mouse epiblast stem cells (EpiSCs). The EpiSC-maintaining medium, which contains Activin A and bFGF, induces differentiation of mouse embryonic stem cells (ESCs) to EpiSCs. Here, we show that Activin A also has an ability to efficiently propagate ESCs without differentiation to EpiSCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28097464/cdc42-promotes-schwann-cell-proliferation-and-migration-through-wnt-%C3%AE-catenin-and-p38-mapk-signaling-pathway-after-sciatic-nerve-injury
#19
Bin Han, Jun-Ying Zhao, Wu-Tao Wang, Zheng-Wei Li, Ai-Ping He, Xiao-Yang Song
Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28096336/%C3%AE-catenin-haploinsufficiency-promotes-mammary-tumorigenesis-in-an-erbb2-positive-basal-breast-cancer-model
#20
Bui Tung, Babette Schade, Robert D Cardiff, Olulanu H Aina, Virginie Sanguin-Gendreau, William J Muller
Aberrant activation of β-catenin through its activity as a transcription factor has been observed in a large proportion of human malignancies. Despite the improved understanding of the β-catenin signaling pathway over the past three decades, attempts to develop therapies targeting β-catenin remain challenging, and none of these targeted therapies have advanced to the clinic. In this study, we show that part of the challenge in antagonizing β-catenin is caused by its dual functionality as a cell adhesion molecule and a signaling molecule...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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