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Juri Bergmann, Miryam Müller, Niklas Baumann, Manuel Reichert, Carola Heneweer, Julia Bolik, Karsten Lücke, Sabine Gruber, Antonella Carambia, Susanne Boretius, Ivo Leuschner, Thomas Becker, Björn Rabe, Johannes Herkel, F Thomas Wunderlich, Hans-Willi Mitrücker, Stefan Rose-John, Dirk Schmidt-Arras
: Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine interleukin 6 (IL-6) is a critical mediator of HCC development. It can signal through two distinct pathways, the IL-6 classic and the IL-6 trans-signaling pathway. While IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Gustavo José Leirós, Julieta María Ceruti, María Lía Castellanos, Ana Gabriela Kusinsky, María Eugenia Balañá
In androgenetic alopecia, androgens impair dermal papilla-induced hair follicle stem cell (HFSC) differentiation inhibiting Wnt signaling. Wnt agonists/antagonists balance was analyzed after dihydrotestosterone (DHT) stimulation in androgen-sensitive dermal papilla cells (DPC) cultured as spheroids or monolayer. In both culture conditions, DHT stimulation downregulated Wnt5a and Wnt10b mRNA while the Wnt antagonist Dkk-1 was upregulated. Notably, tissue architecture of DPC-spheroids lowers Dkk-1 and enhances Wnt agonists' basal expression; probably contributing to DPC inductivity...
October 18, 2016: Molecular and Cellular Endocrinology
Jolanda van Hengel, Celine Van den Broeke, Tim Pieters, Louis Libbrecht, Ilse Hofmann, Frans van Roy
p120 catenin (p120ctn) is required for the stability of classic cadherins at the cell surface and is thought to play a central role in modulating cell-cell adhesion. Cytoplasmic p120ctn promotes cell motility, and probably other activities, by modulating the activities of RhoA, Rac and Cdc42. E-cadherin is expressed in periportal but not in perivenous hepatocytes. In contrast, all hepatocytes of normal mouse liver express N-cadherin. Cholangiocytes express exclusively E-cadherin. Mice with p120ctn ablation in hepatocytes and cholangiocytes (p120LiKO mice) were generated by Cre-loxP technology...
October 15, 2016: European Journal of Cell Biology
Tadamoto Isogai, Rob van der Kammen, Onno B Bleijerveld, Soenita S Goerdayal, Elisabetta Argenzio, A F Maarten Altelaar, Metello Innocenti
Formin mDia2 is a cytoskeleton-regulatory protein that switches reversibly between a closed, auto-inhibited and an open, active conformation. Although the open conformation of mDia2 induces actin assembly thereby controlling many cellular processes, mDia2 possesses also actin-independent and conformation-insensitive scaffolding roles related to microtubules and p53, respectively. Thus, we hypothesise that mDia2 may have other unappreciated functions and regulatory modes. Here we identify and validate proteasome and Ubiquitin as mDia2-interacting partners using SILAC-based quantitative proteomics and biochemistry, respectively...
October 21, 2016: Journal of Proteome Research
Jingjing Yu, Yuling Huang, Lijuan Liu, Jing Wang, Jiye Yin, Lihua Huang, Shaojun Chen, Jingao Li, Hong Yuan, Guoping Yang, Wenyu Liu, Hai Wang, Qi Pei, Chengxian Guo
Radiotherapy (RT) is the normative therapeutic treatment for primary nasopharyngeal carcinoma (NPC). Single nucleotide polymorphisms (SNPs) of genes in Wnt/β-catenin pathway are correlated to the development, prognosis, and treatment benefit of various cancers. However, it has not been established whether SNPs of Wnt/β-catenin pathway are associated with nasopharyngeal tumorigenesis and the efficacy of RT in NPC patients. Therefore, in this study, we aimed to investigate the nine potentially functional SNPs of four genes in the Wnt/β-catenin pathway and genotyped these in 188 NPC patients treated with RT...
October 19, 2016: Oncotarget
Xia Chen, Hua Guo, Fuxia Li, Di Fan
BACKGROUND: The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-β-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis. METHODS: Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of β-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR...
September 13, 2016: Pharmacological Reports: PR
Rebecca L Lamason, Effie Bastounis, Natasha M Kafai, Ricardo Serrano, Juan C Del Álamo, Julie A Theriot, Matthew D Welch
Spotted fever group (SFG) rickettsiae are human pathogens that infect cells in the vasculature. They disseminate through host tissues by a process of cell-to-cell spread that involves protrusion formation, engulfment, and vacuolar escape. Other bacterial pathogens rely on actin-based motility to provide a physical force for spread. Here, we show that SFG species Rickettsia parkeri typically lack actin tails during spread and instead manipulate host intercellular tension and mechanotransduction to promote spread...
October 20, 2016: Cell
Yong-Sik Bong, Shahin Assefnia, Therese Tuohy, Deborah W Neklason, Randall W Burt, Jaeil Ahn, Hao-Wen J Jiang, Stephen W Byers
Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-)...
October 19, 2016: Oncotarget
Gianluigi Franci, Federica Sarno, Angela Nebbioso, Lucia Altucci
Epigenetic modifications are functionally involved in gene expression regulation. In particular, histone posttranslational modifications play a crucial role in functional chromatin organization. Several drugs able to inhibit or stimulate some families of proteins involved in epigenetic histone regulation have been found, a number of which are FDA-approved for the treatment of cutaneous T-cell lymphoma or are in phase I/II/III clinical trials for solid tumors. Although some protein families, such as histone deacetylases and their inhibitors, are well characterized, our understanding of histone lysine demethylases is still incomplete...
October 21, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Wenzel M Hackeng, Elizabeth A Montgomery, Francis M Giardiello, Aatur D Singhi, Marija Debeljak, James R Eshleman, Michael Vieth, G Johan A Offerhaus, Laura D Wood, Lodewijk A A Brosens
BACKGROUND: Gastric pyloric gland adenomas (PGAs) are rare epithelial polyps that are more commonly found in autoimmune atrophic gastritis and familial adenomatous polyposis. Little is known about the morphology and genetics of PGAs in familial adenomatous polyposis. AIMS: PGAs in familial adenomatous polyposis are studied morphologically and genetically. Findings in FAP associated PGAs are compared to sporadic PGAs and related lesions such as oxyntic gland adenoma (OGA) to increase our understanding of these rare polyps...
October 21, 2016: Histopathology
Sajjad Karim, Jaudah A Al-Maghrabi, Hasan M A Farsi, Ahmad J Al-Sayyad, Hans-Juergen Schulten, Abdelbaset Buhmeida, Zeenat Mirza, Alaa A Al-Boogmi, Fai T Ashgan, Manal M Shabaad, Hend F NourEldin, Khalid B M Al-Ghamdi, Adel Abuzenadah, Adeel G A Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. METHODS: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC...
September 30, 2016: BMC Cancer
Kran Suknuntha, Thanyatip Thita, Padma Priya Togarrati, Piyanee Ratanachamnong, Patompon Wongtrakoongate, Sirada Srihirun, Igor Slukvin, Suradej Hongeng
Wnt signaling pathway plays a major role in leukemogenesis of myeloid leukemia. Aberrancy in its regulation results in hyperactivity of the pathway contributing to leukemia propagation and maintenance. To investigate effects of Wnt pathway inhibition in leukemia, we used human leukemia cell lines (i.e., K562, HL60, THP1, and Jurkat) and several Wnt inhibitors, including XAV939, IWP2 and FH535. Our results showed that leukemia cell lines (>95 % cells) had increased endogenous levels of β-catenin as compared to mononuclear cells from healthy donors (0 %)...
October 20, 2016: International Journal of Hematology
C Tsentidis, D Gourgiotis, L Kossiva, A Marmarinos, A Doulgeraki, K Karavanaki
: Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. INTRODUCTION: Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D)...
October 20, 2016: Osteoporosis International
Laura Schirosi, Annalisa Mazzotta, Giuseppina Opinto, Rosamaria Pinto, Giusi Graziano, Stefania Tommasi, Livia Fucci, Giovanni Simone, Anita Mangia
There is an increasing need to identify new biomarkers in colorectal cancer (CRC) to further characterize this malignancy. β-catenin plays a central role in the Wnt signaling pathway. It also binds Na+/H+ exchanger regulating factor 1 (NHERF1) and interacts with the RAS-association domain family 1, isoform A (RASSF1A), but the mechanisms of this possible crosstalk are still not fully understood. In this study, we analyzed for the first time the different subcellular expression of β-catenin, NHERF1, and RASSF1A and their relationships with RASSF1A methylation in the progression of CRC...
September 27, 2016: Oncotarget
Lili Zhang, Marianne Gallup, Lorna Zlock, Yu Ting Feeling Chen, Walter E Finkbeiner, Nancy A McNamara
Lung cancer is the leading cause of cancer-related death, and 87% of these deaths are directly attributable to smoking. Using three-dimensional cultures of primary human bronchial epithelial cells, we demonstrated that loss of adherens junction protein, epithelial cadherin, and the aberrant interaction of its adherens junction binding partner, p120-catenin (p120ctn), with the cytoplasmic tail of apical mucin-1 (MUC1-CT) represent initiating steps in the epithelial-to-mesenchymal transition. Smoke provoked the rapid nuclear entry of p120ctn in complex with MUC1-CT that was inhibited using the MUC1-CT inhibitory peptides, PMIP and GO-201...
October 17, 2016: American Journal of Pathology
Verena Stahn, Inga Nagel, Susan Fischer-Huchzermeyer, Florian Oyen, Reinhard Schneppenheim, Stefan Gesk, Axel Bohring, Levan Chikobava, Peter Young, Burkhard Gess, Mathias Werner, Volker Senner, Anja Harder
Neurofibromas and schwannomas are benign Schwann cell-derived peripheral nerve sheath tumors arising sporadically and within neurofibromatoses. Multiple tumors are a hallmark of neurofibromatosis type 1 (NF1) and type 2 (NF2) and schwannomatosis. Neurofibromas in NF1 and schwannomas in NF2 or schwannomatosis are defined by distinctive molecular hits. Among these, multiple hybrid neurofibromas/schwannomas may also appear, not yet being defined by a molecular background. We therefore performed molecular analysis of 22 hybrid neurofibromas/schwannomas using array comparative genomic hybridization, immunohistochemistry, quantitative RT-PCR, and functional analyses of cultured Schwann cells...
October 17, 2016: American Journal of Pathology
Yoo Seob Shin, Sung Un Kang, Ju Kyeong Park, Yang Eun Kim, Yeon Soo Kim, Seung Joon Baek, Seong-Ho Lee, Chul-Ho Kim
BACKGROUND AND PURPOSE: Aberrant expression of β-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of β-catenin. METHODS: In vitro effects of EGCG on the transcription, translation, or degradation of β-catenin were investigated...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Maryam Dastan, Nowruz Najafzadeh, Ali Abedelahi, Mohammadreza Sarvi, Ali Niapour
Minoxidil and human platelet lysate (HPL) are commonly used to treat patients with hair loss. However, the roles of HPL versus minoxidil in hair follicle biology largely remain unknown. Here, we hypothesized that bulge and dermal papilla (DP) cells may express specific genes, including Kras, Erk, Akt, Shh and β-catenin after exposure to minoxidil or HPL. The mouse hair follicles were isolated on day 10 after depilation and bulge or DP regions were dissected. The bulge and DP cells were cultured for 14days in DMEM/F12 medium...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
QiuShi Wei, Jin Zhang, GuoJu Hong, ZhenQiu Chen, WeiMin Deng, Wei He, Mei Hui Chen
Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yuxia Yang, Yanju Zhang, Zhenchuan Miao, Junhua Zhou, Jianyuan Luo
The bone marrow (BM) microenvironment, heavily composed of osteoblasts, plays a key role during the normal development of hematopoiesis. Endogenous miR-22 has an important function on the hematopoietic development and osteoblastic differentiation. It is unclear whether miR-22 in osteoblasts from the BM microenvironment also has an important function on the development of hematopoiesis. In this study, we found that the capacity of FBMOB-hTERT cells to expand human cord blood (CB) CD34+ cells and maintain the multipotency of CB CD34+ cells is decreased upon ectopic expression of miR-22...
October 20, 2016: Human Gene Therapy
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