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B- catenin

Heather L Lehman, Michal Kidacki, Joshua I Warrick, Douglas B Stairs
Four out of five patients diagnosed with esophageal squamous cell carcinoma (ESCC) will die within five years. This is primarily a result of the aggressive invasive potential of the disease. Our research is focused on the interplay between tumor suppressors and oncogenes in the invasive process. Specifically, EGFR and p120-catenin (p120ctn) are commonly dysregulated genes that are indicative of poor prognosis in ESCC. In a previous study we demonstrated that in our 3D organotypic culture model, only when EGFR overexpression is combined with p120ctn inactivation do the cells transform and invade - as opposed to either event alone...
February 16, 2018: Oncotarget
Takahiro Yoshida, Nikolai A Sopko, Max Kates, Xiaopu Liu, Gregory Joice, David J McConkey, Trinity J Bivalacqua
There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ . Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells...
February 16, 2018: Oncotarget
Yanchun Ma, Kun Chen, Zhenhua Yang, Ming Guan
Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform...
April 2018: Oncology Letters
Peng Yin, Guizhen Song, Zhenhua Jiang
PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytotoxic platinum-based drug used for chemotherapy of different types of human cancers such as NPC. Nevertheless, the effects of CIS on the migration and invasion of human NPC cells and the underlying molecular mechanisms have not yet been fully scrutinized...
March 14, 2018: Cancer Chemotherapy and Pharmacology
Wenjie Deng, Yueyuan Wang, Shuo Zhao, Yujie Zhang, Yan Chen, Xuyang Zhao, Lei Liu, Shixiu Sun, Lin Zhang, Bixing Ye, Jun Du
Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono-oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL1 in breast cancer cell proliferation and to explore the potential molecular mechanism...
March 10, 2018: Journal of Cellular and Molecular Medicine
Genglong Zhu, Xialei Liu, Yonghui Su, Fangen Kong, Xiaopeng Hong, Zhidong Lin
Liver cancer is one of the most common malignancies in the world with a leading cause of cancer-related mortality. Accumulating evidences have highlighted the critical role of long noncoding RNAs (lncRNAs) in various cancers. The present study aimed to explore the role of lncRNA urothelial carcinoma associated 1 (UCA1) in cell growth and migration in MHCC97 cells and its underlying mechanism. Firstly, we assessed the expression of UCA1 in MHCC97 and other three cell lines by qRT-PCR. Then, the expression of UCA1, miR-301a and CXCR4 in MHCC97 cells were altered by transient transfection...
March 9, 2018: Oncology Research
Byoung Hyuck Kim, Hee-Won Jung, Seok Hyun Seo, Hyemi Shin, Jeanny Kwon, Jae Myoung Suh
Unwanted radiological or nuclear exposure remains a public health risk for which effective therapeutic countermeasures are lacking. Here, we evaluated the efficacy of fibroblast growth factor-2 (FGF2) in treating radiation-induced gastrointestinal syndrome (RIGS) incurred by lethal whole-body irradiation (WBI) when administered in conjunction with bone marrow transplantation (BMT). In vitro experiments indicated FGF2 treatment increased proliferation, reduced apoptosis, and upregulated AKT-GSK3β/β-catenin signaling in irradiated IEC-6 cells...
March 7, 2018: Cell Death & Disease
Florence F Wagner, Lina Benajiba, Arthur J Campbell, Michel Weïwer, Joshua R Sacher, Jennifer P Gale, Linda Ross, Alexandre Puissant, Gabriela Alexe, Amy Conway, Morgan Back, Yana Pikman, Ilene Galinsky, Daniel J DeAngelo, Richard M Stone, Taner Kaya, Xi Shi, Matthew B Robers, Thomas Machleidt, Jennifer Wilkinson, Olivier Hermine, Andrew Kung, Adam J Stein, Damodharan Lakshminarasimhan, Michael T Hemann, Edward Scolnick, Yan-Ling Zhang, Jen Q Pan, Kimberly Stegmaier, Edward B Holson
Glycogen synthase kinase 3 (GSK3), a key regulatory kinase in the wingless-type MMTV integration site family (WNT) pathway, is a therapeutic target of interest in many diseases. Although dual GSK3α/β inhibitors have entered clinical trials, none has successfully translated to clinical application. Mechanism-based toxicities, driven in part by the inhibition of both GSK3 paralogs and subsequent β-catenin stabilization, are a concern in the translation of this target class because mutations and overexpression of β-catenin are associated with many cancers...
March 7, 2018: Science Translational Medicine
Hanlin Yao, Zhen Yao, Shaocheng Zhang, Wenjun Zhang, Wen Zhou
Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidative stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/β‑catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type‑1 [sirtuin (SIRT)1]. However, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed...
March 1, 2018: Molecular Medicine Reports
Fernando Gallardo, Joan Bertran, Erika López-Arribillaga, Jéssica González, Silvia Menéndez, Ignacio Sánchez, Luis Colomo, Mar Iglesias, Marta Garrido, Luis Francisco Santamaría-Babí, Ferran Torres, Ramon M Pujol, Anna Bigas, Lluís Espinosa
Cutaneous T-cell lymphomas (CTCLs) represent different subtypes of lymphoproliferative disorders with no curative therapies for the advanced forms of the disease (namely mycosis fungoides and the leukemic variant, Sézary syndrome). Molecular events leading to CTCL progression are heterogeneous, however recent DNA and RNA sequencing studies highlighted the importance of NF-κB and β-catenin pathways. We here show that the kinase TAK1, known as essential in B-cell lymphoma, is constitutively activated in CTCL cells, but tempered by the MYPT1/PP1 phosphatase complex...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Catherine S Grasso, Marios Giannakis, Daniel K Wells, Tsuyoshi Hamada, Xinmeng Jasmine Mu, Michael Quist, Jonathan A Nowak, Reiko Nishihara, Zhi Rong Qian, Kentaro Inamura, Teppei Morikawa, Katsuhiko Nosho, Gabriel Abril-Rodriguez, Charles Connolly, Helena Escuin-Ordinas, Milan S Geybels, William M Grady, Li Hsu, Siwen Hu-Lieskovan, Jeroen R Huyghe, Yeon Joo Kim, Paige E Krystofinski, Mark Dm Leiserson, Dennis J Montoya, Brian B Nadel, Matteo Pellegrini, Colin C Pritchard, Cristina Puig-Saus, Elleanor H Quist, Benjamin J Raphael, Stephen J Salipante, Daniel Sanghoon Shin, Eve Shinbrot, Brian Shirts, Sachet Shukla, Janet L Stanford, Wei Sun, Jennifer Tsoi, Alexander Upfill-Brown, David A Wheeler, Catherine J Wu, Ming Yu, Syed H Zaidi, Jesse M Zaretsky, Stacey B Gabriel, Eric S Lander, Levi A Garraway, Thomas J Hudson, Charles S Fuchs, Antoni Ribas, Shuji Ogino, Ulrike Peters
To understand the genetic drivers of immune recognition and evasion in colorectal cancer (CRC), we analyzed 1,211 CRC primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas CRC cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of CRC, had a high rate of significantly mutated genes in important immune modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy number alterations and copy-neutral loss of heterozygosity (CN-LOH)...
March 6, 2018: Cancer Discovery
Patricia B Maguire, Tim Donlon, Martin Parsons, Kieran Wynne, Eugene Dillon, Fionnuala Ní Áinle, Paulina B Szklanna
We previously demonstrated that the WNT/β-catenin pathway is present and active in platelets and established that the canonical WNT ligand, WNT-3a, suppresses platelet adhesion and activation. In nucleated cells, β-catenin, the key downstream effector of this pathway, is a dual function protein, regulating the coordination of gene transcription and cell-cell adhesion. The specific role of β-catenin in the anucleate platelet however remains elusive. Here, we performed a label-free quantitative proteomic analysis of β-catenin immunoprecipitates from human platelets and identified 9 co-immunoprecipitating proteins...
March 6, 2018: Proteomics
Chao Niu, Li Yin, Haji Akber Aisa
The extracts of Ficuscarica L. and Psoralen corylifolia L. are traditional Uygur medicines for the treatment of vitiligo, and its active ingredients furocoumarins, were are found to be the most effective agents against this skin disorder nowadays. Therefore, a series of novel easter derivatives ( 8a - 8p ) of furocoumarin were designed and synthesized based on our previous research to improve this activity in the present study. The synthesized derivatives were biologically evaluated for melanin synthesis in murine B16 cells and the SAR (structure-activity relationship) was summarized...
March 6, 2018: International Journal of Molecular Sciences
Heqing Wang, Chun Yang, Shengxiang Rao, Yuan Ji, Jing Han, Ruofan Sheng, Mengsu Zeng
PURPOSE: To investigate and compare the MR features between hepatocellular adenoma (HCA) subtypes in China, including preliminary observations on diffusion-weighted imaging (DWI). METHODS: Thirty-six patients with 39 pathologically proven HCAs underwent gadopentetate dimeglumine enhanced MRI. The morphological and imaging features on T1, T2-weighted, dynamic-enhanced imaging and DWI were retrospectively evaluated and compared between four HCA subtypes, using Kruskal-Wallis test, Fisher's exact test and Dunn-Bonferroni post hoc test...
March 2018: European Journal of Radiology
Przemysław Liczbiński, Bożena Bukowska
Amygdalin, named as 'laetrile' and 'vitamin B-17' was initially supposed to be a safe drug for cancer treatment and was recognized by followers of natural medicine since it has been considered to be hydrolyzed only in cancer cells releasing toxic hydrogen cyanide (HCN), and thus destroying them. Unfortunately, current studies have shown that HCN is also released in normal cells, therefore it may not be safe for human organism. However, there have still been research works conducted on anti-cancer properties of this compound...
February 28, 2018: Immunopharmacology and Immunotoxicology
Huijuan Shi, Wenfang Chen, Yu Dong, Xiaofang Lu, Wenhui Zhang, Liantang Wang
To investigate the roles of B‑cell lymphoma‑2 associated athanogene 3 (BAG3) in human chondrosarcoma and the potential mechanisms, the expression levels of BAG3 were detected in the present study, and the associations between BAG3 and clinical pathological parameters, clinical stage as well as the survival of patients were analyzed. The present study detected BAG3 mRNA and protein expression in the normal cartilage cell line HC‑a and in SW1353 chondrosarcoma cells by reverse transcription‑quantitative polymerase chain reaction and western blot analysis...
February 15, 2018: Molecular Medicine Reports
Huda Salman, Xiao Shuai, Anh Thu Nguyen-Lefebvre, Banabihari Giri, Mingqiang Ren, Michael Rauchman, Lynn Robbins, Wei Hou, Hasan Korkaya, Yupo Ma
Similar signaling pathways could operate in both normal hematopoietic stem and progenitor cells (HSPCs) and leukemia stem cells (LSCs). Thus, targeting LSCs signaling without substantial toxicities to normal HSPCs remains challenging. SALL1, is a member of the transcriptional network that regulates stem cell pluripotency, and lacks significant expression in most adult tissues, including normal bone marrow (NBM). We examined the expression and functional characterization of SALL1 in NBM and in acute myeloid leukemia (AML) using in vitro and in vivo assays...
January 26, 2018: Oncotarget
Zhenzhen Zhang, Song Wu, Saeed Muhammad, Qian Ren, Chao Sun
Both miR-103 and 107 have been demonstrated to restrain cell proliferation, regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocytes apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocytes apoptosis. We found that miR-103/107 aggravated Endoplasmic Reticulum (ER) stress mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted Wnt3a (WNT family member 3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes...
February 26, 2018: Journal of Lipid Research
M Shin, M B Chavez, A Ikeda, B L Foster, J D Bartlett
Ameloblasts responsible for enamel formation express matrix metalloproteinase 20 (MMP20), an enzyme that cleaves enamel matrix proteins, including amelogenin (AMELX) and ameloblastin (AMBN). Previously, we showed that continuously erupting incisors from transgenic mice overexpressing active MMP20 had a massive cell infiltrate present within their enamel space, leading to enamel mineralization defects. However, effects of MMP20 overexpression on mouse molars were not analyzed, although these teeth more accurately represent human odontogenesis...
February 1, 2018: Journal of Dental Research
Dong Cui, Yongfu Zhao, Jingchao Xu
Initiation of epithelial-to-mesenchymal transition (EMT) is common in papillary thyroid carcinoma (PTC) and may contribute to its metastasis. Aims of the present study are to investigate whether and how the C-X-C motif chemokine ligand (CXCL)-5/C-X-C motif receptor 2 (CXCR2) axis affects PTC metastasis, with a focus on the EMT process. Herein, two PTC cell lines, KTC-1 and B-CPAP cells, identified as CXCR2-positive cells were used as the cell model. We found that a 24-h stimulation of 1 or 10 nM recombinant human CXCL5 (rhCXCL5) enhanced the migration and invasion of both KTC-1 and B-CPAP cells without affecting their proliferation...
February 19, 2018: Biochimie
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