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https://www.readbyqxmd.com/read/28731043/gastroblastoma-harbors-a-recurrent-somatic-malat1-gli1-fusion-gene
#1
Rondell P Graham, Asha A Nair, Jaime I Davila, Long Jin, Jin Jen, William R Sukov, Tsung-Teh Wu, Henry D Appelman, Jorge Torres-Mora, Kyle D Perry, Lizhi Zhang, Sara M Kloft-Nelson, Ryan A Knudson, Patricia T Greipp, Andrew L Folpe
Gastroblastoma is a rare distinctive biphasic tumor of the stomach. The molecular biology of gastroblastoma has not been studied, and no affirmative diagnostic markers have been developed. We retrieved two gastroblastomas from the consultation practices of the authors and performed transcriptome sequencing on formalin-fixed paraffin-embedded tissue. Recurrent predicted fusion genes were validated at genomic and RNA levels. The presence of the fusion gene was confirmed on two additional paraffin-embedded cases of gastroblastoma...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28726779/maml1-acts-cooperatively-with-gli-proteins-to-regulate-sonic-hedgehog-signaling-pathway
#2
Roberta Quaranta, Maria Pelullo, Sabrina Zema, Francesca Nardozza, Saula Checquolo, Dieter Matthias Lauer, Francesca Bufalieri, Rocco Palermo, Maria Pia Felli, Alessandra Vacca, Claudio Talora, Lucia Di Marcotullio, Isabella Screpanti, Diana Bellavia
Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (GCPs) and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma. The effects of Shh pathway are mediated by the Gli family of transcription factors, which controls the expression of a number of target genes, including Gli1. Here, we identify Mastermind-like 1 (Maml1) as a novel regulator of the Shh signaling since it interacts with Gli proteins, working as a potent transcriptional coactivator...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28722677/prognostic-role-of-gli1-expression-in-breast-cancer-a-meta-analysis
#3
Bilan Wang, Ting Yu, Yuzhu Hu, Mengmeng Xiang, Haoning Peng, Yunzhu Lin, Lu Han, Lingli Zhang
Glioma-associated oncogene 1 (Gli1) is a critical transcriptional factor of Sonic hedgehog pathway which has been proved to participate in the initiation and progression of tumor in mammalians. However, its clinical value in breast cancer remains unknown. Thus, a meta-analysis was performed to clarify the association of Gli1 over-expression, clinic-pathological characteristics, molecular subtypes and prognosis in breast cancer. According to included criteria, 13 eligible studies containing 2816 patients all around the world were selected in this study...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720477/nanoquinacrine-caused-apoptosis-in-oral-cancer-stem-cells-by-disrupting-the-interaction-between-gli1-and-%C3%AE-catenin-through-activation-of-gsk3%C3%AE
#4
Anmada Nayak, Sumit Siddharth, Sarita Das, Deepika Nayak, Chinmayee Sethy, Chanakya Nath Kundu
Presences of cancer stem cells (CSCs) in a bulk of cancer cells are responsible for tumor relapse, metastasis and drug resistance in oral cancer. Due to high drug efflux, DNA repair and self-renewable capacity of CSCs, the conventional chemotherapeutic agents are unable to kill the CSCs. CSCs utilizes Hedgehog (HH-GLI), WNT-β catenin signalling for its growth and development. GSK3β negatively regulates both the pathways in CSCs. Here, we have shown that a nano-formulated bioactive small molecule inhibitor Quinacrine (NQC) caused apoptosis in oral cancer stem cells (OCSCs; isolated from different oral cancer cells and oral cancer patient derived primary cells) by down regulating WNT-β catenin and HH-GLI components through activation of GSK3β...
July 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28717663/refining-genotype-phenotype-correlation-in-alstr%C3%A3-m-syndrome-through-study-of-primary-human-fibroblasts
#5
Jian-Hua Chen, Tarekegn Geberhiwot, Timothy G Barrett, Richard Paisey, Robert K Semple
BACKGROUND: Alström syndrome (AS), featuring retinal dystrophy, neuronal deafness, cardiomyopathy, metabolic syndrome, and diffuse fibrosis, is caused by biallelic mutations in the centrosomal protein ALMS1. Genotype-phenotype correlation has been suggested without assessment of ALMS1 expression. METHODS: ALMS1 expression (real-time PCR and immunocytochemistry) and cilia formation (immunocytochemistry) were assessed in fibroblasts from deeply phenotyped volunteers diagnosed with AS recruited from a dedicated AS Service...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28716052/%C3%AE-arrestin1-mediated-acetylation-of-gli1-regulates-hedgehog-gli-signaling-and-modulates-self-renewal-of-shh-medulloblastoma-cancer-stem-cells
#6
Evelina Miele, Agnese Po, Federica Begalli, Laura Antonucci, Angela Mastronuzzi, Carlo Efisio Marras, Andrea Carai, Danilo Cucchi, Luana Abballe, Zein Mersini Besharat, Giuseppina Catanzaro, Paola Infante, Lucia Di Marcotullio, Gianluca Canettieri, Enrico De Smaele, Isabella Screpanti, Franco Locatelli, Elisabetta Ferretti
BACKGROUND: Aberrant Sonic Hedgehog/Gli (Hh/Gli) signaling pathway is a critical regulator of Sonic hedgehog medulloblastoma (SHH-MB). Cancer stem cells (CSCs), thought to be largely responsible for tumor initiation, maintenance, dissemination and relapse, have been identified in SHH-MB. Since we previously demonstrated that Hh/Gli signaling controls CSCs features in SHH-MB and that in these tumors miR-326 is down regulated, here we investigated whether there is a functional link between Hh/Gli signaling and miR-326...
July 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28703798/mtorc2-regulates-hedgehog-pathway-activity-by-promoting-stability-to-gli2-protein-and-its-nuclear-translocation
#7
Samarpan Maiti, Susmita Mondal, Eswara M Satyavarapu, Chitra Mandal
mTORC2 is aberrantly activated in cancer and therefore is considered to be an important therapeutic target. The hedgehog pathway, which is also often hyperactivated, regulates transcription of several genes associated with angiogenesis, metastasis, cellular proliferation and cancer stem cell (CSC) regeneration. However, the contribution of mTORC2 toward hedgehog pathway activity has not been explored yet. Here we have addressed the molecular cross talk between mTORC2 and hedgehog pathway activities in the context of glioblastoma multiforme, a malignant brain tumor using as a model system...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28690072/identity-of-gli1-cells-in-the-bone-marrow
#8
REVIEW
Isadora Sena, Pedro Prazeres, Gabryella Santos, Isabella Borges, Patrick Azevedo, Julia Andreotti, Viviani Almeida, Ana Paiva, Daniel Guerra, Luiza Lousado, Luanny Souto, Akiva Mintz, Alexander Birbrair
Bone marrow fibrosis is a critical component of primary myelofibrosis in which normal bone marrow tissue and blood-forming cells are gradually replaced with scar tissue. The specific cellular and molecular mechanisms that cause bone marrow fibrosis are not understood. A recent study by using state-of-the-art techniques including in vivo lineage-tracing provides evidence that Gli1+ cells are the cells responsible for fibrotic disease in the bone marrow. Strikingly, genetic depletion of Gli1+ cells rescues bone marrow failure and abolishes myelofibrosis...
July 6, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28686747/functional-analysis-of-the-zebrafish-ortholog-of-hmgcs1-reveals-independent-functions-for-cholesterol-and-isoprenoids-in-craniofacial-development
#9
Anita M Quintana, Jose A Hernandez, Cesar G Gonzalez
There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions...
2017: PloS One
https://www.readbyqxmd.com/read/28668841/itraconazole-modulates-hedgehog-wnt-%C3%AE-catenin-as-well-as-akt-signalling-and-inhibits-proliferation-of-cervical-cancer-cells
#10
Tomoko Ueda, Hiroshi Tsubamoto, Kayo Inoue, Kazuko Sakata, Hiroaki Shibahara, Takashi Sonoda
BACKGROUND/AIM: Repurposing itraconazole as an anticancer agent has been evaluated in several studies. The present study investigated whether itraconazole exerts an anticancer effect on cervical cancer cells. MATERIALS AND METHODS: CaSki and HeLa cells were cultured in itraconazole and vehicle after which colony-forming and cell viability assays were performed. Transcription and protein expression were assessed by cDNA microarray analysis and immunoblotting, respectively...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28664474/intratumoral-heterogeneity-of-frameshift-mutations-of-gli1-encoding-a-hedgehog-signaling-protein-in-colorectal-cancers
#11
Ju Hwa Lee, Sang Yong Song, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee
GLI1 is a transcription factor for hedgehog signaling that plays a crucial role in signaling pathways for controlling cell proliferation, alterations of which are known to contribute to tumorigenesis. Aim of this study was to explore whether GLI1 gene is mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that GLI1 had a G7 mononucleotide repeat in the coding sequences that could be a mutation target in the cancers with microsatellite instability (MSI). In this study, we analyzed frameshift mutation of GLI1 in 79 GCs and 129 CRCs (high MSI (MSI-H) or microsatellite stable (MSS)) by single-strand conformation polymorphism analysis and DNA sequencing...
June 29, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28652248/gli1-blockade-potentiates-the-antitumor-activity-of-pi3k-antagonists-in-lung-squamous-cell-carcinoma
#12
Sahba Kasiri, Chunli Shao, Baozhi Chen, Alexandra N Wilson, Paul Yenerall, Brenda C Timmons, Luc Girard, Hui Tian, Carmen Behrens, Ignacio I Wistuba, Adi F Gazdar, James Kim
Lung squamous cell carcinoma (SCC), strongly associated with smoking, is treated primarily with traditional cytotoxic chemotherapy due to a lack of FDA-approved targeted agents available. Here we identify the Hedgehog pathway transcription factor GLI1 as a critical driver of lung SCC. Analysis of human lung cancer datasets showed that GLI1 mRNA was highly expressed in human lung SCC and portended a poor prognosis. Inhibition of GLI1 in human lung SCC cell lines suppressed tumor cell clonogenicity and proliferation in culture and in vivo...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645539/gli1-labeled-adult-mesenchymal-stem-progenitor-cells-and-hedgehog-signaling-contribute-to-endochondral-heterotopic-ossification
#13
Chen Kan, Lijun Chen, Yangyang Hu, Na Ding, Yuyun Li, Tammy L McGuire, Haimei Lu, John A Kessler, Lixin Kan
Heterotopic ossification (HO), acquired or hereditary, endochondral or intramembranous, is the formation of true bone outside the normal skeleton. Since perivascular Gli1+ progenitors contribute to injury induced organ fibrosis, and CD133 is expressed by a variety of populations adult stem cells, this study utilized Cre-lox based genetic lineage tracing to test the contribution to endochondral HO of adult stem/progenitor cells that expressed either Gli1 or CD133. We found that both lineages contributed broadly to different normal tissues with distinct patterns, but that only Gli1-creERT labeled stem/progenitor cells contributed to all stages of endochondral HO in a BMP dependent, injury induced, transgenic mouse model...
June 20, 2017: Bone
https://www.readbyqxmd.com/read/28635133/critical-role-of-glioma-associated-oncogene-homolog-1-in-maintaining-invasive-and-mesenchymal-like-properties-of-melanoma-cells
#14
I Ketut Gunarta, Rong Li, Ryota Nakazato, Ryusuke Suzuki, Jambaldorj Boldbaatar, Takeshi Suzuki, Katsuji Yoshioka
Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non-invasive and invasive potentials, and microphthalmia-associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma-associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear...
June 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28631844/sonic-hedgehog-wnt-and-brain-derived-neurotrophic-factor-cell-signaling-pathway-crosstalk-potential-therapy-for-depression
#15
REVIEW
Mohd Tayyab, Mehdi H Shahi, Shirin Farheen, Mubeena P M Mariyath, Nabeela Khanam, Javier S Castresana, M Mobarak Hossain
There are various theories to explain the pathophysiology of depression and support its diagnosis and treatment. The roles of monoamines, brain-derived neurotrophic factor (BDNF), and Wnt signaling are well researched, but sonic hedgehog (Shh) signaling and its downstream transcription factor Gli1 are not well studied in depression. Shh signaling plays a fundamental role in embryonic development and adult hippocampal neurogenesis and also involved in the growth of cancer. In this article, we summarize the evidence for the Shh signaling pathway in depression and the potential crosstalk of Shh with Wnt and BDNF...
June 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28630282/desumoylation-of-gli1-by-senp1-attenuates-sonic-hedgehog-signaling
#16
Huaize Liu, Sen Yan, Jie Ding, Ting-Ting Yu, Steven Y Cheng
Transcriptional output of the Sonic hedgehog morphogenic pathway is orchestrated by three Krüppel family transcription factors, Gli1-3, which undergo extensive post-translational modifications, including ubiquitination and SUMOylation. Here, we report that sentrin-specific peptidase SENP1 is the specific de-SUMOylation enzyme for Gli1. We show that SUMOylation stabilizes Gli1 by competing with ubiquitination at conserved lysine residues, and SUMOylated Gli1 is enriched in the nucleus, suggesting that SUMOylation is a nuclear localization signal for Gli1...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28623188/gli1-induced-deubiquitinase-usp48-aids-glioblastoma-tumorigenesis-by-stabilizing-gli1
#17
Aidong Zhou, Kangyu Lin, Sicong Zhang, Li Ma, Jianfei Xue, Saint-Aaron Morris, Kenneth D Aldape, Suyun Huang
Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28604738/emt-cells-increase-breast-cancer-metastasis-via-paracrine-gli-activation-in-neighbouring-tumour-cells
#18
Deepika Neelakantan, Hengbo Zhou, Michael U J Oliphant, Xiaomei Zhang, Lukas M Simon, David M Henke, Chad A Shaw, Meng-Fen Wu, Susan G Hilsenbeck, Lisa D White, Michael T Lewis, Heide L Ford
Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28600143/involvement-of-pi3k-akt-pathway-in-the-inhibition-of-hepatocarcinoma-cell-invasion-and-metastasis-induced-by-sash1-through-downregulating-shh-gli1-signaling
#19
Changyu Sun, Zhihao Zhang, Ping He, Yan Zhou, Xuhua Xie
The SASH1 gene is discovered as a tumor suppressor recently. However, the molecular mechanisms of SASH1 in hepatocarcinoma (HCC) remain unclear. In present studies, we investigated the molecular mechanisms of SASH1 on cell invasion and metastasis of hepatocarcinoma in vivo and in vitro. In this study, SASH1 overexpression HCC cell lines were treated with purmorphamine (0, 0.5, 1, 2μmol/l). Western blot and qRT-PCR were used to examine the related gene expression of EMT markers and the Shh-Gli1 and PI3K/Akt-dependent pathway...
June 7, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28583401/mir-873-suppresses-h9c2-cardiomyocyte-proliferation-by-targeting-gli1
#20
REVIEW
Jing-Shu Zhang, Yue Zhao, Yuan Lv, Pei-Yan Liu, Jun-Xia Ruan, Yue-Ling Sun, Tian-Xing Gong, Nan Wan, Guang-Rong Qiu
MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs that regulate the expression of target genes. Previous studies have suggested that miRNAs are key regulators in cardiovascular systems. This study investigated the role of miR-873 in H9C2 cardiomyocytes by targeting glioma-associated oncogene 1 (GLI1). miR-873 was significantly up-regulated in serum samples from congenital heart disease (CHD) patients compared with those from normal individuals. Furthermore, miR-873 over-expression suppressed H9C2 proliferation and induced cell cycle arrest...
June 2, 2017: Gene
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