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https://www.readbyqxmd.com/read/29149105/lgr5-expression-is-regulated-by-egf-in-early-colorectal-adenomas-and-governs-egfr-inhibitor-sensitivity
#1
R G Morgan, E Mortensson, D N Legge, B Gupta, T J Collard, A Greenhough, A C Williams
BACKGROUND: LGR5 serves as a co-receptor for Wnt/β-catenin signalling and marks normal intestinal stem cells; however, its role in colorectal cancer (CRC) remains controversial. LGR5(+) cells are known to exist outside the stem cell niche during CRC progression, and the requirement for epidermal growth factor (EGF) signalling within early adenomas remains to be fully elucidated. METHODS: Epidermal growth factor and gefitinib treatments were performed in EGF-responsive LGR5(+) early adenoma RG/C2 cells...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29133594/competitive-kinase-enrichment-proteomics-reveals-that-abemaciclib-inhibits-gsk3%C3%AE-and-activates-wnt-signaling
#2
Emily M Cousins, Dennis Goldfarb, Feng Yan, Jose Roques, David B Darr, Gary L Johnson, Michael B Major
The cellular and organismal phenotypic response to a small-molecule kinase inhibitor is defined collectively by the inhibitor's targets and their functions. The selectivity of small-molecule kinase inhibitors is commonly determined in vitro, using purified kinases and substrates. Recently, competitive chemical proteomics has emerged as a complementary, unbiased, cell-based methodology to define the target landscape of kinase inhibitors. Here, we evaluated and optimized a competitive multiplexed inhibitor bead mass spectrometry (MIB/MS) platform using cell lysates, live cells, and treated mice...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133142/dedifferentiated-endometrial-carcinomas-with-neuroendocrine-features-a-clinicopathologic-immunohistochemical-and-molecular-genetic-study
#3
Iñigo Espinosa, Antonio De Leo, Emanuela D'Angelo, Juan M Rosa-Rosa, Marina Corominas, Alan Gonzalez, José Palacios, Jaime Prat
Undifferentiated endometrial carcinoma is an aggressive type of uterine cancer which is occasionally associated with a low-grade endometrioid carcinoma component. This combination is referred to as "dedifferentiated endometrioid endometrial carcinoma." Neuroendocrine expression may occur in undifferentiated endometrial carcinoma but its significance in dedifferentiated endometrial carcinomas is unknown. To gain insight into the pathogenesis of these tumors we have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, b-catenin, SMARCB1, synaptophysin, chromogranin A, and CD56) and mutational status (PTEN, KRAS, PIK3CA, TP53 and POLE) of 4 dedifferentiated endometrial carcinomas with strong and diffuse neuroendocrine expression...
November 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/29130932/p120-catenin-is-an-obligate-haploinsufficient-tumor-suppressor-in-intestinal-neoplasia
#4
Sarah P Short, Jumpei Kondo, Whitney G Smalley-Freed, Haruna Takeda, Michael R Dohn, Anne E Powell, Robert H Carnahan, Mary K Washington, Manish Tripathi, D Michael Payne, Nancy A Jenkins, Neal G Copeland, Robert J Coffey, Albert B Reynolds
p120-Catenin (p120) functions as a tumor suppressor in intestinal cancer, but the mechanism is unclear. Here, using conditional p120 knockout in Apc-sensitized mouse models of intestinal cancer, we have identified p120 as an "obligatory" haploinsufficient tumor suppressor. Whereas monoallelic loss of p120 was associated with a significant increase in tumor multiplicity, loss of both alleles was never observed in tumors from these mice. Moreover, forced ablation of the second allele did not further enhance tumorigenesis, but instead induced synthetic lethality in combination with Apc loss of heterozygosity...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29129760/the-key-role-of-proinflammatory-cytokines-matrix-proteins-rankl-opg-and-wnt-%C3%AE-catenin-in-bone-healing-of-hip-arthroplasty-patients
#5
Jean Cassuto, Agnetha Folestad, Jan Göthlin, Henrik Malchau, Johan Kärrholm
INTRODUCTION: We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. MATERIALS AND METHODS: Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs...
November 9, 2017: Bone
https://www.readbyqxmd.com/read/29128706/consumption-of-ellagic-acid-and-dihydromyricetin-synergistically-protects-against-uv-b-induced-photoaging-possibly-by-activating-both-tgf-%C3%AE-1-and-wnt-signaling-pathways
#6
Na Rang Moon, Suna Kang, Sunmin Park
Ellagic acid (EGA) and dihydromyricetin (DHM) are both found in fruits and vegetables are used for anti-aging treatment for the skin. The anti-photoaging efficacy of EGA and DHM was investigated in UV-B irradiated skin in vivo and the involvement of transforming growth factor (TGF)-β1 and wnt signaling pathways were examined in vitro. HaCaT cells were treated with either 50μM EGA, 50μM DHM or 25μM EGA+25μM DHM before 100mJ/cm(2) UV-B exposure, and then oxidative stress and inflammation was measured. The involvement of TGF-β1 and wnt signaling was measured using their inhibitors, respectively, in HaCaT cells...
November 7, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29124284/ca-2-nuclear-factor-of-activated-t-cells-signaling-is-enriched-in-early-onset-rectal-tumors-devoid-of-canonical-wnt-activation
#7
Raju Kumar, Ratheesh Raman, Viswakalyan Kotapalli, Swarnalata Gowrishankar, Saumyadipta Pyne, Jonathan R Pollack, Murali D Bashyam
Our previous extensive analysis revealed a significant proportion of early-onset colorectal tumors from India to be localized to the rectum in younger individuals and devoid of deregulated Wnt/β-catenin signaling. In the current study, we performed a comprehensive genome-wide analysis of clinically well-annotated microsatellite stable early-onset sporadic rectal cancer (EOSRC) samples. Results revealed extensive DNA copy number alterations in rectal tumors in the absence of deregulated Wnt/β-catenin signaling...
November 9, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29118542/the-role-of-the-endothelin-axis-in-promoting-epithelial-to-mesenchymal-transition-and-lymph-node-metastasis-in-prostate-adenocarcinoma
#8
Sophia Papanikolaou, Vasiliki Bravou, Helen Papadaki, Kostis Gyftopoulos
Introduction: Aberrant activation of endothelin (ET) axis has been identified as a key player in tumor growth and metastasis in several tumor types. However, little is known about the possible interaction of the ET with epithelial to mesenchymal transition (EMT), a process that transforms tumor cells in a motile, resistant to apoptosis phenotype prone to invasion and metastasis. The aim of this study was to investigate the activation of the ET axis in prostate adenocarcinoma and examine possible associations with EMT markers, lymph node (LN) metastasis, and other clinicopathological parameters...
October 2017: Urology Annals
https://www.readbyqxmd.com/read/29115442/golph3-expression-promotes-the-resistance-of-ht29-cells-to-5%C3%A2-fluorouracil-by-activating-multiple-signaling-pathways
#9
Ming-Zhen Wang, Cheng-Zhi Qiu, Wai-Shi Yu, Yan-Ta Guo, Chun-Xiao Wang, Zhi-Xiong Chen
The novel proto‑oncogene Golgi phosphoprotein (GOLPH)3 is overexpressed in a variety of tumor tissues and is associated with poor prognosis. The authors previously demonstrated that GOLPH3 gene is overexpressed in colorectal cancer tissues and promotes the proliferation of colonic cancer cells by activating the phosphatidylinositol‑3‑kinase/protein kinase B/the mammalian target of rapamycin and Wnt/β‑catenin signaling pathways. However, to the best of the authors' knowledge, if and how the GOLPH3 gene is involved in inducing resistance to colonic cancer chemotherapy has not been reported...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115291/maintenance-of-neural-progenitor-cell-stemness-in-3d-hydrogels-requires-matrix-remodelling
#10
Christopher M Madl, Bauer L LeSavage, Ruby E Dewi, Cong B Dinh, Ryan S Stowers, Margarita Khariton, Kyle J Lampe, Duong Nguyen, Ovijit Chaudhuri, Annika Enejder, Sarah C Heilshorn
Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from ∼0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness...
October 30, 2017: Nature Materials
https://www.readbyqxmd.com/read/29113952/do-all-roads-lead-to-the-rome-the-glycation-perspective
#11
REVIEW
Saheem Ahmad, Firoz Akhter, Uzma Shahab, Zeeshan Rafi, Mohd Sajid Khan, Rabia Nabi, Mohd Salman Khan, Khurshid Ahmad, Jalaluddin Mohammad Ashraf, Moinuddin
Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (HIF-1α), β-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules...
November 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29108761/esculetin-attenuates-the-growth-of-lung-cancer-by-downregulating-wnt-targeted-genes-and-suppressing-nf-%C3%AE%C2%BAb
#12
Xiangyun Zhu, Jiaping Gu, Hongxian Qian
INTRODUCTION: Esculetin was identified to inhibit cell proliferation and induce apoptosis or cell cycle arrest in several cancer cell lines. However, the effect of esculetin on lung cancer remains elusive. METHODS: The anti-proliferative role of esculetin in murine Lewis lung carcinoma (LLC) cells was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays. BALB/c mice were subcutaneously injected with LLC cells to investigate the inhibitory effect of esculetin on the growth of lung cancer xenograft...
November 3, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/29108673/%C3%AE-catenin-acts-in-a-position-independent-regeneration-response-in-the-simple-eumetazoan-hydra
#13
S Gufler, B Artes, H Bielen, I Krainer, M-K Eder, J Falschlunger, A Bollmann, T Ostermann, T Valovka, M Hartl, K Bister, U Technau, B Hobmayer
Wnt/β-Catenin signaling plays crucial roles in regenerative processes in eumetazoans. It also acts in regeneration and axial patterning in the simple freshwater polyp Hydra, whose morphallactic regenerative capacity is unparalleled in the animal kingdom. Previous studies have identified β-catenin as an early response gene activated within the first 30min in Hydra head regeneration. Here, we have studied the role of β-Catenin in more detail. First, we show that nuclear β-Catenin signaling is required for head and foot regeneration...
September 21, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29108267/beta-catenin-represses-protein-kinase-d1-gene-expression-by-non-canonical-pathway-through-myc-max-transcription-complex-in-prostate-cancer
#14
Bita Nickkholgh, Sivanandane Sittadjody, Michael B Rothberg, Xiaolan Fang, Kunzhao Li, Jeff W Chou, Gregory A Hawkins, K C Balaji
Down regulation of Protein Kinase D1 (PrKD1), a novel serine threonine kinase, in prostate, gastric, breast and colon cancers in humans leads to disease progression. While the down regulation of PrKD1 by DNA methylation in gastric cancer and by nuclear beta-catenin in colon cancer has been shown, the regulatory mechanisms in other cancers are unknown. Because we had demonstrated that PrKD1 is the only known kinase to phosphorylate threonine 120 (T120) of beta-catenin in prostate cancer resulting in increased nuclear beta-catenin, we explored the role of beta-catenin in gene regulation of PrKD1...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106415/evolution-and-clinical-impact-of-co-occurring-genetic-alterations-in-advanced-stage-egfr-mutant-lung-cancers
#15
Collin M Blakely, Thomas B K Watkins, Wei Wu, Beatrice Gini, Jacob J Chabon, Caroline E McCoach, Nicholas McGranahan, Gareth A Wilson, Nicolai J Birkbak, Victor R Olivas, Julia Rotow, Ashley Maynard, Victoria Wang, Matthew A Gubens, Kimberly C Banks, Richard B Lanman, Aleah F Caulin, John St John, Anibal R Cordero, Petros Giannikopoulos, Andrew D Simmons, Philip C Mack, David R Gandara, Hatim Husain, Robert C Doebele, Jonathan W Riess, Maximilian Diehn, Charles Swanton, Trever G Bivona
A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers...
November 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29104081/wnt-pathway-activator-tws119-enhances-the-proliferation-and-cytolytic-activity-of-human-%C3%AE-%C3%AE-t-cells-against-colon-cancer
#16
Yong-Qiang Chen, Lu Zheng, Mohanad Aldarouish, Zhong-Hai Zhou, Ning Pan, Jun-Quan Liu, Fu-Xing Chen, Li-Xin Wang
γδT cells are a distinct T-cell subset that display unique characteristics regarding T-cell receptor gene usage, tissue tropism and antigen recognition. Adoptive γδT cell transfer therapy has recently been gaining importance as an efficient approach in cancer immunotherapy. However, exploiting γδT cell response for tumour immunotherapy is a challenge due to cell numbers, activities and differentiation states that minimize the clinical therapeutic effects. Previous studies have indicated that the wnt/β-catenin signalling pathway plays a crucial role in the differentiation, survival and enhancement of the immune response of T lymphocytes...
November 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29095481/biallelic-mutations-in-flnb-cause-a-skeletal-dysplasia-with-46-xy-gonadal-dysgenesis-by-activating-%C3%AE-catenin
#17
K Upadhyay, J Loke, V O, B Taragin, H Ostrer
Filamin B (FLNB) functions as a switch that can affect chrondrocyte development and endochondral bone formation through a series of signaling molecules and transcription factors that also affect Sertoli cell development. Here, we report a subject with a novel skeletal dysplasia and co-existing 46,XY gonadal dysgenesis and biallelic mutations in FLNB. Whole exome sequencing was performed to identify mutations. Quantitative qPCR and flow variant assays were performed to quantify RNA, proteins and phosphorylated proteins...
November 2, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/29091324/lncrna-expression-profiles-in-hbv-transformed-human-hepatocellular-carcinoma-cells-treated-with-a-novel-inhibitor-of-human-la-protein
#18
Jiaqian Pan, Shuangmei Tong, Jing Tang
We previously identified a novel inhibitor of La protein, H11, which inhibited hepatitis B virus (HBV) replication by inhibiting the interaction between La protein and HBV RNA. However, the other cellular factors involved in this process remain unclear. To investigate the mechanism of H11-mediated inhibition of HBV infection, a lncRNA microarray analysis was performed using H11-treated and untreated stable HBV-expressing human hepatoblastoma HepG2.2.15 cells. The profiles of differentially expressed lncRNAs and mRNAs were generated and analyzed using Gene Ontology (GO) and pathway analyses...
November 1, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29071717/sox8-regulates-cancer-stem-like-properties-and-cisplatin-induced-emt-in-tongue-squamous-cell-carcinoma-by-acting-on-the-wnt-%C3%AE-catenin-pathway
#19
S-L Xie, S Fan, S-Y Zhang, W-X Chen, Q-X Li, G-K Pan, H-Q Zhang, W-W Wang, B Weng, Z Zhang, J-S Li, Z-Y Lin
A sub-population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumour relapse and metastasis. In this study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin-resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin-resistant TSCC cells, which displayed CSC-like properties and exhibited EMT...
October 26, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29070526/circulating-tumors-cells-from-different-vascular-sites-exhibit-spatial-heterogeneity-in-epithelial-and-mesenchymal-composition-and-distinct-clinical-significance-in-hepatocellular-carcinoma
#20
Yunfan Sun, Wei Guo, Yang Xu, Ying-Hong Shi, Zijun Gong, Yuan Ji, Min Du, Xin Zhang, Bo Hu, Ao Huang, George G Chen, Paul B S Lai, Ya Cao, Shuang-Jian Qiu, Jian Zhou, Xin-Rong Yang, Jia Fan
PURPOSE: The spatial heterogeneity of phenotypic and molecular characteristics of CTCs within circulatory system remains unclear. Herein, we mapped the distribution and characterized biological features of CTCs along the transportation route in hepatocellular carcinoma (HCC).  Experimental Design: In 73 localized HCC patients, blood was drawn from peripheral vein (PV), peripheral artery (PA), hepatic veins (HV), infrahepatic inferior vena cava (IHIVC) and portal vein (PoV) before tumor resection...
October 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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