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https://www.readbyqxmd.com/read/28429760/corrigendum-selective-targeting-of-hdac1-2-elicits-anticancer-effects-through-gli1-acetylation-in-preclinical-models-of-shh-medulloblastoma
#1
Sonia Coni, Anna Barbara Mancuso, Laura Di Magno, Giulia Sdruscia, Simona Manni, Silvia Maria Serrao, Dante Rotili, Eleonora Spiombi, Francesca Bufalieri, Marialaura Petroni, Monika Kusio-Kobialka, Enrico De Smaele, Elisabetta Ferretti, Carlo Capalbo, Antonello Mai, Pawel Niewiadomski, Isabella Screpanti, Lucia Di Marcotullio, Gianluca Canettieri
No abstract text is available yet for this article.
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28418873/combined-inhibition-of-gli-and-flt3-signaling-leads-to-effective-anti-leukemic-effects-in-human-acute-myeloid-leukemia
#2
Emily-Marie Latuske, Hauke Stamm, Marianne Klokow, Gabi Vohwinkel, Jana Muschhammer, Carsten Bokemeyer, Manfred Jücker, Maxim Kebenko, Walter Fiedler, Jasmin Wellbrock
Activation of the Hedgehog pathway has been implicated in the pathogenesis of several tumor types including myeloid leukemia. Previously we demonstrated that overexpression of Hedgehog downstream mediators GLI1/2 confers an adverse prognosis to patients with acute myeloid leukemia (AML) and is correlated with a FLT3 mutated status. To analyze a possible non-canonical activation of the Hedgehog pathway via FLT3 and PI3K, we performed blocking experiments utilizing inhibitors for FLT3 (sunitinib), PI3K (PF-04691502) and GLI1/2 (GANT61) in FLT3-mutated and FLT3 wildtype AML cell lines and primary blasts...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417299/negative-prognostic-effect-of-low-nuclear-gli1-expression-in-glioblastomas
#3
Yuil Kim, In-Gu Do, Mineui Hong, Yeon-Lim Suh
The hedgehog signaling plays supportive roles in various aspects of tumorigenesis. Increased expression of the key component, GLI1, has been shown to correlate with poor prognosis in many types of cancers. We aimed to investigate the effect of GLI1 expression in glioblastoma focusing on the nuclear localization. Immunohistochemistry for GLI1, GLI2, PTCH1, SMO, and SHH were done in 140 glioblastoma tissues, and the staining was graded. For GLI1, nuclear and cytoplasmic expression was separately assessed. No significant correlation was found between clinicopathologic parameters and expression grades of the five proteins...
April 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28413604/the-role-of-gli1-for-5-fu-resistance-in-colorectal-cancer
#4
Lining Zhang, Ruolan Song, Dongsheng Gu, Xiaoli Zhang, Beiqin Yu, Bingya Liu, Jingwu Xie
Colorectal cancer is a leading cause of cancer-related mortality worldwide, with Fluorouracil (5-FU)-based chemotherapy as the major treatment for advanced disease. Many patients with advanced colorectal cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. Thus, identifying molecular mechanisms responsible for chemotherapy resistance will help design novel strategies to treat colorectal cancer. In this study, we established an acquired 5-FU resistant cell line, LoVo-R, from LoVo cells...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28412462/spop-regulates-gli3-activity-and-shh-signaling-in-dorsoventral-patterning-of-the-mouse-spinal-cord
#5
Hongchen Cai, Aimin Liu
Sonic Hedgehog (Shh) signaling regulates the patterning of ventral spinal cord through the effector Gli family of transcription factors. Previous in vitro studies showed that an E3 ubiquitin ligase containing Speckle-type POZ protein (Spop) targets Gli2 and Gli3 for ubiquitination and degradation, but the role of Spop in Shh signaling and mammalian spinal cord patterning remains unknown. Here, we show that loss of Spop does not alter spinal cord patterning, but it suppresses the loss of floor plate and V3 interneuron phenotype of Gli2 mutants, suggesting a negative role of Spop in Gli3 activator activity, Shh signaling and the specification of ventral cell fates in the spinal cord...
April 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28404967/gli1-mediated-regulation-of-side-population-is-responsible-for-drug-resistance-in-gastric-cancer
#6
Beiqin Yu, Dongsheng Gu, Xiaoli Zhang, Jianfang Li, Bingya Liu, Jingwu Xie
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Chemotherapy is frequently used for gastric cancer treatment. Most patients with advanced gastric cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. Thus, identifying molecular mechanisms responsible for cancer relapse following chemotherapy will help design new ways to treat gastric cancer. In this study, we revealed that the residual cancer cells following treatment with chemotherapeutic reagent cisplatin have elevated expression of hedgehog target genes GLI1, GLI2 and PTCH1, suggestive of hedgehog signaling activation...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399898/itraconazole-induces-apoptosis-and-cell-cycle-arrest-via-inhibiting-hedgehog-signaling-in-gastric-cancer-cells
#7
Qiang Hu, Yi-Chao Hou, Jiao Huang, Jing-Yuan Fang, Hua Xiong
BACKGROUND: Itraconazole has been proved therapeutically effective against a variety of human cancers. This study assessed the effect of itraconazole on the Hedgehog (Hh) pathway and proliferation of human gastric cancer cells. METHODS: CCK-8 assay and colony formation assay were used to assess the effects of itraconazole on proliferation of gastric cancer cells. The expression of Hh signaling components in gastric cancer cells treated with itraconazole was evaluated by reverse-transcription polymerase chain reaction, immunoblotting and dual luciferase assay...
April 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28393230/the-mechanism-of-epithelial-mesenchymal-transition-induced-by-tgf-%C3%AE-1-in-neuroblastoma-cells
#8
Jing-Bo Shao, Zhi-Mei Gao, Wen-Yan Huang, Zhi-Bao Lu
Neuroblastoma is the second most common extracranial malignant solid tumor that occurs in childhood, and metastasis is one of the major causes of death in neuroblastoma patients. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. Therefore, this study investigated the mechanism by which transforming growth factor (TGF)-β1 induces EMT in human neuroblastoma cells. Using quantitative RT-qPCR and western blot analyses, we found that the mRNA and protein expression levels of E-cadherin were significantly decreased, whereas that of α-SMA was significantly increased after neuroblastoma cells were treated with different concentrations of TGF-β1...
April 5, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28390897/identification-and-characterization-of-two-novel-ptch1-splice-variants
#9
Pei Yu, Jinqing Yang, Yan Zhang
Patched-1 (PTCH1), one of the key molecules involved in the Hedgehog (HH) signaling pathway, acts as the receptor of the HH ligand. PTCH1 also inhibits the positive signal transducer Smoothened (SMO). Several PTCH1 splice variants have been identified and confirmed to play critical roles in HH pathway regulation. In the present study, two novel alternatively spliced variants of PTCH1 transcripts, designated PTCH1-Δ10 and PTCH1-Δ15, were found in humans, mice and zebrafish using RT-PCR, direct sequencing and ribonuclease protection assays...
April 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28380428/penfluridol-suppresses-glioblastoma-tumor-growth-by-akt-mediated-inhibition-of-gli1
#10
Alok Ranjan, Sanjay K Srivastava
Glioblastoma (GBM) is the most common brain tumor with poor survival rate. Our results show that penfluridol, an antipsychotic drug significantly reduced the survival of ten adult and pediatric glioblastoma cell lines with IC50 ranging 2-5 μM after 72 hours of treatment and induced apoptosis. Penfluridol treatment suppressed the phosphorylation of Akt at Ser473 and reduced the expression of GLI1, OCT4, Nanog and Sox2 in several glioblastoma cell lines in a concentration-dependent manner. Inhibiting Akt with LY294002 and siRNA, or inhibiting GLI1 using GANT61, cyclopamine, siRNA and CRISPR/Cas9 resulted in enhanced cell growth suppressive effects of penfluridol...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379718/sonic-hedgehog-signaling-regulates-myofibroblast-function-during-alveolar-septum-formation-in-murine-postnatal-lung
#11
Matthias C Kugler, Cynthia A Loomis, Zhicheng Zhao, Jennifer C Cushman, Li Liu, John S Munger
Sonic Hedgehog (Shh) signaling regulates mesenchymal proliferation and differentiation during embryonic lung development. In the adult lung, Shh signaling maintains mesenchymal quiescence and is dysregulated in diseases such as IPF and COPD. Our previous data implicated a role for Shh in postnatal lung development. Here we report a detailed analysis of Shh signaling during murine postnatal lung development. We show that Shh pathway expression and activity during alveolarization (P0-P14) are distinct from those during maturation (P14-P24)...
April 5, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28379358/loss-of-dynein-2-intermediate-chain-wdr34-results-in-defects-in-retrograde-ciliary-protein-trafficking-and-hedgehog-signaling-in-the-mouse
#12
Chuanqing Wu, Jia Li, Andrew Peterson, Kaixiong Tao, Baolin Wang
The Wdr34 gene encodes an intermediate chain of cytoplasmic dynein 2, the motor for retrograde intraflagellar transport (IFT) in primary cilia. Although mutations in human WDR34 have recently been reported, the association of WDR34 function with Hedgehog (Hh) signaling has not been established, and actual cilia defects in the WDR34 mutant cells have also not been completely characterized. In the present study, we show that Wdr34 mutant mice die in midgestation and exhibit open brain and polydactyly phenotypes...
March 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28370670/origin-and-characterization-of-alpha-smooth-muscle-actin-positive-cells-during-murine-lung-development
#13
Alena Moiseenko, Vahid Kheirollahi, Cho-Ming Chao, Negah Ahmadvand, Jennifer Quantius, Jochen Wilhelm, Susanne Herold, Katrin Ahlbrecht, Rory E Morty, Albert A Rizvanov, Parviz Minoo, Elie El Agha, Saverio Bellusci
ACTA2 expression identifies pulmonary airway and vascular smooth muscle cells (SMCs) as well as alveolar myofibroblasts (MYF). Mesenchymal progenitors expressing fibroblast growth factor 10 (Fgf10), Wilms tumor 1 (Wt1), or glioma-associated oncogene 1 (Gli1) contribute to SMC formation from early stages of lung development. However, their respective contribution and specificity to the SMC and/or alveolar MYF lineages remain controversial. In addition, the contribution of mesenchymal cells undergoing active WNT signaling remains unknown...
April 3, 2017: Stem Cells
https://www.readbyqxmd.com/read/28368412/noncanonical-gli1-signaling-promotes-stemness-features-and-in-vivo-growth-in-lung-adenocarcinoma
#14
A Po, M Silvano, E Miele, C Capalbo, A Eramo, V Salvati, M Todaro, Z M Besharat, G Catanzaro, D Cucchi, S Coni, L Di Marcotullio, G Canettieri, A Vacca, G Stassi, E De Smaele, M Tartaglia, I Screpanti, R De Maria, E Ferretti
Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28365245/induced-mir-1249-expression-by-aberrant-activation-of-hedegehog-signaling-pathway-in-hepatocellular-carcinoma
#15
Yibiao Ye, Yunping Wei, Yunxiuxiu Xu, Yanshan Li, Ruomei Wang, Jie Chen, Yu Zhou, Zhiqiang Fu, Yan Chen, Xin Wang, Ruiping Yu, Chunling Bai, Guangpeng Li, Rufu Chen, Tao Chen
Aberrant activations of Hedegehog (Hh) signaling were found in hepatocellular carcinoma (HCC) and some other cancer types. However, the details have not been completely understood and the underlying mechanism remains unclear. Here we reported that miR-1249 transcription in HCC cells was regulated through direct binding to the conserved sequences in miR-1249 promoter region by Gli1, which functions as a transcription factor and is a component in the Hh signaling pathway. Interestingly, expression of tumor suppressor PTCH1, which is another component of the Hh signaling pathway, was inhibited by miR-1249 through targeting its 3'-untranslated region...
March 30, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28363830/hedgehog-signaling-contributes-to-basic-fibroblast-growth-factor-regulated-fibroblast-migration
#16
Zhong Xin Zhu, Cong Cong Sun, Yu Ting Zhu, Ying Wang, Tao Wang, Li Sha Chi, Wan Hui Cai, Jia Yong Zheng, Xuan Zhou, Wei Tao Cong, Xiao Kun Li, Li Tai Jin
Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2...
March 28, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28339981/transcriptome-analysis-of-comb-and-testis-from-rose-comb-silky-chicken-r1-r1-and-beijing-fatty-wild-type-chicken-r-r
#17
Y Wang, J Li, C Feng, Y Zhao, X Hu, N Li
Rose-comb was one of the chicken comb-variants first used by Bateson and Punnet in 1902 to demonstrate Mendelian inheritance in animals. Rose-comb is a monogenic trait that has been widely described in chickens. It is caused by a large structural rearrangement that leads to mis-expression of transcription factor MNR2 on chromosome 7. Rose-comb has pleiotropic effects in homozygous roosters, which is associated with poor sperm mobility. It was postulated that this is caused by the disruption of the CCDC108 gene located at the distal inversion breakpoint...
March 2, 2017: Poultry Science
https://www.readbyqxmd.com/read/28317088/phase-i-trial-of-the-oral-smoothened-inhibitor-sonidegib-in-combination-with-paclitaxel-in-patients-with-advanced-solid-tumors
#18
A Stathis, D Hess, R von Moos, K Homicsko, G Griguolo, M Joerger, M Mark, C J Ackermann, S Allegrini, C V Catapano, A Xyrafas, M Enoiu, S Berardi, P Gargiulo, C Sessa
Purpose To establish a recommended phase II dose (RP2D) for the oral smoothened inhibitor sonidegib in combination with paclitaxel; secondary objectives include evaluation of safety, tolerability, markers of Hedgehog (Hh) signaling and preliminary antitumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating sonidegib dose levels (400mg, 600mg and 800mg orally, once daily on days 1-28) in combination with paclitaxel 80 mg/m(2) on days 1, 8 and 15 in 4-weekly cycles. Dose-limiting toxicities (DLTs) were assessed using CTCAE v4...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28302010/discovery-of-hedgehog-antagonists-for-cancer-therapy
#19
Harleen Khatra, Chandra Bose, Surajit Sinha
BACKGROUND: The evolutionarily conserved Hedgehog (Hh) signaling cascade is one of the key mediators of embryonic development of many metazoans. This pathway has been extensively targeted by small molecule inhibitors as its misregulation leads to various malignancies and developmental disorders. Thus, blocking this pathway can be a novel therapeutic avenue for the treatment of Hedgehog-dependent cancers. This review covers the mechanism of hedgehog signaling in vertebrate cells, provides an overview of reported small molecule Hh pathway inhibitors, with the synthetic routes and SAR studies of some of them discussed briefly...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28286162/gli1-expression-in-cancer-stem-like-cells-predicts-poor-prognosis-in-patients-with-lung-squamous-cell-carcinoma
#20
Yan Cui, Chun-Ai Cui, Zhao-Ting Yang, Wei-Dong Ni, Yu Jin, Yan-Hua Xuan
PURPOSE: Glioma-associated oncogene homolog 1 (Gli1) is involved in cancer stem cell (CSC) maintenance in various tumors; however, its expression and clinical significance in lung squamous cell carcinoma (LSCC) has not been reported. In this study, we aimed to reveal the clinical significance of Gli1 in LSCC and investigate the potential of Gli1 as a CSC marker by comparing its expression with that of other stemness-related genes in LSCC. METHODS: We assessed the expressions of Gli1, LSD1, CD44, Sox9 and Sox2 by immunohistochemistry in the tissue specimens obtained from 101 patients with LSCC...
March 9, 2017: Experimental and Molecular Pathology
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