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https://www.readbyqxmd.com/read/28726779/maml1-acts-cooperatively-with-gli-proteins-to-regulate-sonic-hedgehog-signaling-pathway
#1
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/28723639/integrated-analysis-of-the-molecular-action-of-vorinostat-identifies-epi-sensitised-targets-for-combination-therapy
#2
Jodie F Hay, Katrina Lappin, Fabio Liberante, Laura M Kettyle, Kyle B Matchett, Alexander Thompson, Ken I Mills
Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment...
July 1, 2017: Oncotarget
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
#3
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/28715412/cell-fate-specification-in-the-lingual-epithelium-is-controlled-by-antagonistic-activities-of-sonic-hedgehog-and-retinoic-acid
#4
Maha El Shahawy, Claes-Göran Reibring, Cynthia L Neben, Kristina Hallberg, Pauline Marangoni, Brian D Harfe, Ophir D Klein, Anders Linde, Amel Gritli-Linde
The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28714964/inhibition-of-wnt-signaling-attenuates-self-renewal-of-shh-subgroup-medulloblastoma
#5
J Rodriguez-Blanco, L Pednekar, C Penas, B Li, V Martin, J Long, E Lee, W A Weiss, C Rodriguez, N Mehrdad, D M Nguyen, N G Ayad, P Rai, A J Capobianco, D J Robbins
The SMOOTHENED inhibitor vismodegib is FDA approved for advanced basal cell carcinoma (BCC), and shows promise in clinical trials for SONIC HEDGEHOG (SHH)-subgroup medulloblastoma (MB) patients. Clinical experience with BCC patients shows that continuous exposure to vismodegib is necessary to prevent tumor recurrence, suggesting the existence of a vismodegib-resistant reservoir of tumor-propagating cells. We isolated such tumor-propagating cells from a mouse model of SHH-subgroup MB and grew them as sphere cultures...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28713553/the-evolution-of-medulloblastoma-therapy-to-personalized-medicine
#6
REVIEW
Soma Sengupta, Daniel Pomeranz Krummel, Scott Pomeroy
Recent advances in cancer genomics have revolutionized the characterization and classification of medulloblastomas. According to the current WHO guidelines, medulloblastomas are now classified into the following molecularly defined groups: Wnt signaling pathway (WNT)-activated, sonic hedgehog signaling pathway (SHH)-activated and tumor suppressor protein p53 (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH (i.e. group 3 and group 4). Importantly, genomic, epigenomic, and proteomic advances have created a potential paradigm shift in therapeutic options...
2017: F1000Research
https://www.readbyqxmd.com/read/28710291/two-types-of-etiological-mutation-in-the-limb-specific-enhancer-of-shh
#7
Takanori Amano, Tomoko Sagai, Ryohei Seki, Toshihiko Shiroishi
An enhancer named MFCS1 regulates Sonic hedgehog (Shh) expression in the posterior mesenchyme of limb buds. Several mutations in MFCS1 induce ectopic Shh expression in the anterior limb bud, and these result in preaxial polydactyly (PPD). However, the molecular basis of ectopic Shh expression remains elusive, although some mutations are known to disrupt the negative regulation of Shh expression in the anterior limb bud. Here, we analyzed the molecular mechanism of ectopic Shh expression in PPD including in a mouse mutation-hemimelic extra toes (Hx)-and in other MFCS1 mutations in different species...
July 14, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28708091/trail-wnt-sonic-hedgehog-tgf%C3%AE-and-mirna-signalings-are-potential-targets-for-oral-cancer-therapy
#8
REVIEW
Ammad Ahmad Farooqi, Chih-Wen Shu, Hurng-Wern Huang, Hui-Ru Wang, Yung-Ting Chang, Sundas Fayyaz, Shyng-Shiou F Yuan, Jen-Yang Tang, Hsueh-Wei Chang
Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy...
July 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28707430/multi-genic-pattern-found-in-rare-type-of-hypopituitarism-a-whole-exome-sequencing-study-of-han-chinese-with-pituitary-stalk-interruption-syndrome
#9
Qing-Hua Guo, Cheng-Zhi Wang, Zhi-Qiang Wu, Yan Qin, Bai-Yu Han, An-Ping Wang, Bao-An Wang, Jing-Tao Dou, Xiao-Sheng Wu, Yi-Ming Mu
Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis...
July 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28706295/dgk%C3%AE-triggers-endoplasmic-reticulum-release-of-ift88-containing-vesicles-destined-for-the-assembly-of-primary-cilia
#10
Jie Ding, Lei Shao, Yixing Yao, Xin Tong, Huaize Liu, Shen Yue, Lu Xie, Steven Y Cheng
The morphogenic factor Sonic hedgehog (Shh) signals through the primary cilium, which relies on intraflagellar transport to maintain its structural integrity and function. However, the process by which protein and lipid cargos are delivered to the primary cilium from their sites of synthesis still remains poorly characterized. Here, we report that diacylglycerol kinase δ (DGKδ), a residential lipid kinase in the endoplasmic reticulum, triggers the release of IFT88-containing vesicles from the ER exit sites (ERES), thereby setting forth their movement to the primary cilium...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706234/investigation-of-brain-tissue-infiltration-by-medulloblastoma-cells-in-an-ex-vivo-model
#11
Anuja Neve, Karthiga Santhana Kumar, Dimitra Tripolitsioti, Michael A Grotzer, Martin Baumgartner
Medulloblastoma (MB) is a paediatric cancer of the cerebellum that can develop cerebellar and leptomeningeal metastases. Local brain tissue infiltration, the underlying cause of metastasis and relapse, remains unexplored. We developed a novel approach to investigate tissue infiltration of MB using organotypic cerebellum slice culture (OCSC). We show that cellular and structural components of cerebellar tissue in OCSCs are maintained for up to 30 days ex vivo, and that OCSCs foster tumour growth and cell proliferation...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697535/cancer-stem-cells-and-epithelial-mesenchymal-transition-in-urothelial-carcinoma-possible-pathways-and-potential-therapeutic-approaches
#12
REVIEW
Dong Fang, Hiroshi Kitamura
There is growing evidence of the presence of cancer stem cells in urothelial carcinoma. Cancer stem cells have the ability to self-renew and to differentiate into all cell types of the original heterogeneous tumor. A panel of diverse cancer stem cell markers might be suitable for simulation studies of urothelial cancer stem cells and for the development of optimized treatment protocols. The present review focuses on the advances in recognizing the markers of urothelial cancer stem cells and possible therapeutic targets...
July 11, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28695340/tropomyosin-receptor-kinase-c-trkc-expression-in-medulloblastoma-relation-to-the-molecular-subgroups-and-impact-on-treatment-response
#13
Carsten Friedrich, Tarek Shalaby, Christoph Oehler, Martin Pruschy, Burkhardt Seifert, Daniel Picard, Marc Remke, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Stefan Rutkowski, Michael A Grotzer, André O von Bueren
PURPOSE: High messenger RNA (mRNA) expression of the tropomyosin receptor kinase C gene (TrkC) has been associated with favorable survival in medulloblastoma patients. Untested is whether it plays a role through modulating the response to therapy or whether it might be a surrogate marker for a favorable molecular subgroup. METHODS: The medulloblastoma-derived cell line DAOY was stably transfected to overexpress TrkC (clone DAOY-TrkC) and compared to a control (clone DAOY-EV, empty vector transfected)...
July 10, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28690477/identity-by-descent-refines-mapping-of-candidate-regions-for-preaxial-polydactyly-ii-iii-in-a-large-chinese-pedigree
#14
Xingyan Yang, Quankuan Shen, Xierzhatijiang Sulaiman, Hequn Liu, Minsheng Peng, Yaping Zhang
Preaxial polydactyly (PPD) is congenital hand malformation characterized by the duplication of digit. Herein, we scan the genome-wide SNPs for a large Chinese family with PPD-II/III. We employ the refined IBD algorithm to identify the identity-by-decent (IBD) segments and compare the frequency among the patients and normal relatives. A total of 72 markers of 0.01 percentile of the permutation are identified as the peak signals. Among of them, 57markers locate on chromosome 7q36 which is associated with PPD...
2018: Hereditas
https://www.readbyqxmd.com/read/28686747/functional-analysis-of-the-zebrafish-ortholog-of-hmgcs1-reveals-independent-functions-for-cholesterol-and-isoprenoids-in-craniofacial-development
#15
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/28684624/cell-interactions-signals-and-transcriptional-hierarchy-governing-placode-progenitor-induction
#16
Mark Hintze, Ravindra Singh Prajapati, Monica Tambalo, Nicolas A D Christophorou, Maryam Anwar, Timothy Grocott, Andrea Streit
In vertebrates, cranial placodes contribute to all sense organs and sensory ganglia and arsise from a common pool of Six1/Eya2+ progenitors. Here we dissect the events that specify ectodermal cells as placode progenitors using newly identified genes upstream of the Six/Eya complex. We show that two different tissues, the lateral head mesoderm and the prechordal mesendoderm, gradually induce placode progenitors: cells pass through successive transcriptional states, each identified by distinct factors and controlled by different signals...
July 6, 2017: Development
https://www.readbyqxmd.com/read/28684360/regulator-of-g-protein-signaling-5-rgs5-inhibits-sonic-hedgehog-function-in-mouse-cortical-neurons
#17
Chuanliang Liu, Qiongqiong Hu, Jia Jing, Yun Zhang, Jing Jin, Liulei Zhang, Lili Mu, Yumei Liu, Bo Sun, Tongshuai Zhang, Qingfei Kong, Guangyou Wang, Dandan Wang, Yao Zhang, Xijun Liu, Wei Zhao, Jinghua Wang, Tao Feng, Hulun Li
Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth...
July 3, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28681415/transcriptional-changes-in-chick-wing-bud-polarization-induced-by-retinoic-acid
#18
Joseph Pickering, Neha Wali, Matthew Towers
BACKGROUND: Retinoic acid is implicated in the induction of the gene encoding Sonic hedgehog (Shh) that specifies antero-posterior positional values and promotes growth of the developing limb bud. However, because retinoic acid is involved in limb initiation, it has been difficult to determine if it could have additional roles in antero-posterior patterning. To investigate this, we implanted retinoic acid-soaked beads to the anterior margin of the chick wing bud and performed microarray analyses prior to onset of Shh expression...
July 6, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28679037/biopolymer-molecular-weight-can-modulate-the-wound-healing-efficacy-of-multivalent-sonic-hedgehog-hyaluronic-acid-conjugates
#19
Taylor A Holstlaw, Mavish Mahomed, Livia W Brier, David M Young, Nancy J Boudreau, Wesley M Jackson
There is a clinical need for new therapeutics to improve healing of chronic impaired wounds. Thus, we investigated how biopolymer conjugation could be used to improve the wound healing performance of a key growth factor for tissue regeneration: Sonic hedgehog (Shh). We generated two multivalent Shh conjugates (mvShh) using hyaluronic acid with two different MWs, which exhibited equivalent potency and proteolytic protection in vitro. Using db/db diabetic mice, we showed that mvShh made with smaller HyA MW resulted in more rapid and robust neovascularization compared to mvShh made with larger MW HyA...
July 5, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28678189/reduction-of-asthmatic-parameters-by-sea-hare-hydrolysates-in-a-mouse-model-of-allergic-asthma
#20
Ji Hyeon Ryu, Chengliang Xie, Eun-Jin Kim, Si-Hyang Park, Yeung Joon Choi, Sang Soo Kang, Min-Kyoung Shin, Dawon Kang
Sea hare has a variety of biological activities. However, little is known regarding the anti-asthmatic effects of sea hare. This study was performed to identify the effect of sea hare hydrolysates (SHH) on an ovalbumin (OVA)-induced allergic asthma model. The experimental asthma model was sensitized and challenged with OVA. We found that a high-dose of SHH (HSHH) significantly inhibited OVA-induced airway inflammation and mucus production around the airway in lung sections, while low- and medium-dose SHH showed an insignificant effect...
July 5, 2017: Nutrients
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