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Hedgehog signalling pathway

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https://read.qxmd.com/read/30769952/the-importance-of-the-hedgehog-signaling-pathway-in-tumorigenesis-of-spinal-and-cranial-chordoma
#1
Reza Akhavan-Sigari, Walter Schulz-Schaeffer, Amanda Angelika Harcej, Veit Rohde
Chordomas is rare malignant bone tumors thought to arise from remnants of embryonic notochord along the spine, frequently at the skull base and sacrum. Although chordoma is slow growing tumors, while are extremely recurrent, and aggressive, as well as the rate of prognosis remains poorly. Radical surgery and high-dose radiation are the most used treatments. Currently, there is no effective chemotherapeutic standard for chordomas. The Hedgehog (HH) pathway adjusts various processes included in expansion and differentiation of tissues and organs throughout the fetus's life, furthermore cell growth and differentiation in the adult organism, of the cell in an adult organism, in which acute anesthesia is involved in multiple cancers...
February 15, 2019: Journal of Clinical Medicine
https://read.qxmd.com/read/30769097/prss23-knockdown-inhibits-gastric-tumorigenesis-through-eif2-signaling
#2
Bing Han, Yang Yang, Jiang Chen, Xingxing He, Nonghua Lv, Runwei Yan
PRSS23 is a newly discovered serine protease that has been associated with tumor progression in various types of cancers. Our previous study showed PRSS23 is down-regulated obviously in Hedgehog pathway blocked gastric cancer cells. However, the correlation between PRSS23 and tumor progression of gastric cancer remains unclear. Here, the role and mechanism of PRSS23 in tumor progression of gastric cancer were determined. PRSS23 protein levels were significantly increased in gastric cancer tissues compared with the paired adjacent normal gastric mucosa tissues...
February 12, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/30766964/hedgehog-signaling-modulates-interleukin-33-dependent-extrahepatic-bile-duct-cell-proliferation-in-mice
#3
Nataliya Razumilava, Junya Shiota, Nureen H Mohamad Zaki, Ramon Ocadiz-Ruiz, Christine M Cieslak, Kais Zakharia, Benjamin L Allen, Gregory J Gores, Linda C Samuelson, Juanita L Merchant
Hedgehog (HH) signaling participates in hepatobiliary repair after injury and is activated in patients with cholangiopathies. Cholangiopathies are associated with bile duct (BD) hyperplasia, including expansion of peribiliary glands, the niche for biliary progenitor cells. The inflammation-associated cytokine interleukin (IL)-33 is also up-regulated in cholangiopathies, including cholangiocarcinoma. We hypothesized that HH signaling synergizes with IL-33 in acute inflammation-induced BD hyperplasia. We measured extrahepatic BD (EHBD) thickness and cell proliferation with and without an IL-33 challenge in wild-type mice, mice overexpressing Sonic HH ( pCMV-Shh ), and mice with loss of the HH pathway effector glioma-associated oncogene 1 ( Gli1lacZ/lacZ )...
February 2019: Hepatology Communications
https://read.qxmd.com/read/30765517/opposite-regulation-of-wnt-%C3%AE-catenin-and-shh-signaling-pathways-by-rack1-controls-mammalian-cerebellar-development
#4
Haihong Yang, Qian Zhu, Juanxian Cheng, Yan Wu, Ming Fan, Jiyan Zhang, Haitao Wu
The development of the cerebellum depends on intricate processes of neurogenesis, migration, and differentiation of neural stem cells (NSCs) and progenitor cells. Defective cerebellar development often results in motor dysfunctions and psychiatric disorders. Understanding the molecular mechanisms that underlie the complex development of the cerebellum will facilitate the development of novel treatment options. Here, we report that the receptor for activated C kinase (Rack1), a multifaceted signaling adaptor protein, regulates mammalian cerebellar development in a cell type-specific manner...
February 14, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30764875/genetic-deletion-of-genes-in-the-cerebellar-rhombic-lip-lineage-can-stimulate-compensation-through-adaptive-reprogramming-of-ventricular-zone-derived-progenitors
#5
Alexandre Wojcinski, Morgane Morabito, Andrew K Lawton, Daniel N Stephen, Alexandra L Joyner
BACKGROUND: The cerebellum is a foliated posterior brain structure involved in coordination of motor movements and cognition. The cerebellum undergoes rapid growth postnataly due to Sonic Hedgehog (SHH) signaling-dependent proliferation of ATOH1+ granule cell precursors (GCPs) in the external granule cell layer (EGL), a key step for generating cerebellar foliation and the correct number of granule cells. Due to its late development, the cerebellum is particularly vulnerable to injury from preterm birth and stress around birth...
February 14, 2019: Neural Development
https://read.qxmd.com/read/30761741/eif5a-regulates-proliferation-and-chemoresistance-in-pancreatic-cancer-through-the-shh-signalling-pathway
#6
Zheng Wang, Jie Jiang, Tao Qin, Ying Xiao, Liang Han
BACKGROUND: Pancreatic cancer (PC) has a very poor prognosis and comparatively short survival. Eukaryotic translation initiation factor 5A (EIF5A) promotes cancer metastasis. Here, we exploited the biological role of EIF5A in PC chemoresistance. METHODS: Expression of EIF5A was analysed in PC cells and tissues by real-time PCR, Western blotting, immunohistochemistry and immunofluorescent. EIF5A expression was specifically suppressed by transfection, and subsequently the alterations of growth behaviour and resistance to anticancer treatment were tested in an orthotopic tumour model...
February 14, 2019: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/30754726/polyamine-metabolism-as-a-therapeutic-target-inhedgehog-driven-basal-cell-carcinomaand-medulloblastoma
#7
REVIEW
Sonia Coni, Laura Di Magno, Silvia Maria Serrao, Yuta Kanamori, Enzo Agostinelli, Gianluca Canettieri
Hedgehog (Hh) signaling is a critical developmental regulator and its aberrant activation,due to somatic or germline mutations of genes encoding pathway components, causes Basal CellCarcinoma (BCC) and medulloblastoma (MB). A growing effort has been devoted at theidentification of druggable vulnerabilities of the Hedgehog signaling, leading to the identificationof various compounds with variable efficacy and/or safety. Emerging evidence shows that anaberrant polyamine metabolism is a hallmark of Hh-dependent tumors and that itspharmacological inhibition elicits relevant therapeutic effects in clinical or preclinical models ofBCC and MB...
February 11, 2019: Cells
https://read.qxmd.com/read/30754706/gli-proteins-regulation-in-development-and-cancer
#8
REVIEW
Paweł Niewiadomski, Sylwia M Niedziółka, Łukasz Markiewicz, Tomasz Uśpieński, Brygida Baran, Katarzyna Chojnowska
Gli proteins are transcriptional effectors of the Hedgehog signaling pathway. They play key roles in the development of many organs and tissues, and are deregulated in birth defects and cancer. We review the molecular mechanisms of Gli protein regulation in mammals, with special emphasis on posttranslational modifications and intracellular transport. We also discuss how Gli proteins interact with co-activators and co-repressors to fine-tune the expression of Hedgehog target genes. Finally, we provide an overview of the regulation of developmental processes and tissue regeneration by Gli proteins and discuss how these proteins are involved in cancer progression, both through canonical regulation via the Hedgehog pathway and through cross-talk with other signaling pathways...
February 11, 2019: Cells
https://read.qxmd.com/read/30744607/ligustrazin-increases-lung-cell-autophagy-and-ameliorates-paraquat-induced-pulmonary-fibrosis-by-inhibiting-pi3k-akt-mtor-and-hedgehog-signalling-via-increasing-mir-193a-expression
#9
Ming-Wei Liu, Mei-Xian Su, Deng-Yun Tang, Li Hao, Xiang-Han Xun, Yun-Qiao Huang
BACKGROUND: Reactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis...
February 11, 2019: BMC Pulmonary Medicine
https://read.qxmd.com/read/30742991/transcriptome-analysis-after-ppar%C3%AE-activation-in-human-meibomian-gland-epithelial-cells-hmgec
#10
Sun Woong Kim, Donald J Brown, James V Jester
PURPOSE: PPARγ plays a critical role in the maturation of immortalized human meibomian gland epithelial cells (hMGEC). To further understand the molecular changes associated with meibocyte differentiation, we analyzed transcriptome profiles from hMGEC after PPARγ activation. METHODS: Three sets of cultivated hMGEC with or without exposure to PPARγ agonist, rosiglitazone were used for RNA-seq analysis. RNA was isolated and processed to generate 6 libraries. The libraries were then sequenced and mapped to the human reference genome, and the expression results were gathered as reads per length of transcript in kilobases per million mapped reads (RPKM) values...
February 8, 2019: Ocular Surface
https://read.qxmd.com/read/30741348/diagnosis-and-management-of-basal-cell-carcinoma
#11
REVIEW
Keiji Tanese
Basal cell carcinomas (BCCs) are common skin cancers that tend to appear on sun-exposed skin. Pathobiologically, activation of the Hedgehog signaling pathway characterizes the majority of cases. In general, BCCs are slow-growing and rarely metastasize. Nevertheless, they are locally invasive and can be destructive. While typical cases are diagnosed based on clinical findings, the clinicopathological manifestations are varied. Consequently, skin biopsy is essential to confirm the diagnosis and evaluate the risk of recurrence...
February 11, 2019: Current Treatment Options in Oncology
https://read.qxmd.com/read/30736319/regulation-of-survivin-isoform-expression-by-gli-proteins-in-ovarian-cancer
#12
Diana Trnski, Maja Gregorić, Sonja Levanat, Petar Ozretić, Nikolina Rinčić, Tajana Majić Vidaković, Držislav Kalafatić, Ivana Maurac, Slavko Orešković, Maja Sabol, Vesna Musani
Ovarian cancer (OC) is the most lethal female gynecological malignancy, mostly due to diagnosis in late stages when treatment options are limited. Hedgehog-GLI (HH-GLI) signaling is a major developmental pathway involved in organogenesis and stem cell maintenance, and is activated in OC. One of its targets is survivin ( BIRC5 ), an inhibitor of apoptosis protein (IAP) that plays a role in multiple processes, including proliferation and cell survival. We wanted to investigate the role of different GLI proteins in the regulation of survivin isoform expression (WT, 2α, 2B, 3B, and Δex3) in the SKOV-3 OC cell line...
February 6, 2019: Cells
https://read.qxmd.com/read/30733609/cellular-signalling-by-primary-cilia-in-development-organ-function-and-disease
#13
REVIEW
Zeinab Anvarian, Kirk Mykytyn, Saikat Mukhopadhyay, Lotte Bang Pedersen, Søren Tvorup Christensen
Primary cilia project in a single copy from the surface of most vertebrate cell types; they detect and transmit extracellular cues to regulate diverse cellular processes during development and to maintain tissue homeostasis. The sensory capacity of primary cilia relies on the coordinated trafficking and temporal localization of specific receptors and associated signal transduction modules in the cilium. The canonical Hedgehog (HH) pathway, for example, is a bona fide ciliary signalling system that regulates cell fate and self-renewal in development and tissue homeostasis...
February 7, 2019: Nature Reviews. Nephrology
https://read.qxmd.com/read/30733525/enabling-precision-medicine-by-unravelling-disease-pathophysiology-quantifying-signal-transduction-pathway-activity-across-cell-and-tissue-types
#14
Anja van de Stolpe, Laurent Holtzer, Henk van Ooijen, Marcia Alves de Inda, Wim Verhaegh
Signal transduction pathways are important in physiology and pathophysiology. Targeted drugs aim at modifying pathogenic pathway activity, e.g., in cancer. Optimal treatment choice requires assays to measure pathway activity in individual patient tissue or cell samples. We developed a method enabling quantitative measurement of functional pathway activity based on Bayesian computational model inference of pathway activity from measurements of mRNA levels of target genes of the pathway-associated transcription factor...
February 7, 2019: Scientific Reports
https://read.qxmd.com/read/30733505/ipse-a-urogenital-parasite-derived-immunomodulatory-protein-ameliorates-ifosfamide-induced-hemorrhagic-cystitis-through-downregulation-of-pro-inflammatory-pathways
#15
Evaristus C Mbanefo, Loc Le, Rebecca Zee, Nirad Banskota, Kenji Ishida, Luke F Pennington, Justin I Odegaard, Theodore S Jardetzky, Abdulaziz Alouffi, Franco H Falcone, Michael H Hsieh
Ifosfamide and other oxazaphosphorines can result in hemorrhagic cystitis, a constellation of complications caused by acrolein metabolites. We previously showed that a single dose of IPSE (Interleukin-4-inducing principle from Schistosoma eggs), a schistosome-derived host modulatory protein, can ameliorate ifosfamide-related cystitis; however, the mechanisms underlying this urotoxicity and its prevention are not fully understood. To provide insights into IPSE's protective mechanism, we undertook transcriptional profiling of bladders from ifosfamide-treated mice, with or without pretreatment with IPSE or IPSE-NLS (a mutant of IPSE lacking nuclear localization sequence)...
February 7, 2019: Scientific Reports
https://read.qxmd.com/read/30723576/inhibition-of-hedgehog-signaling-reprograms-the-dysfunctional-immune-microenvironment-in-breast-cancer
#16
Ann Hanna, Brandon J Metge, Sarah K Bailey, Dongquan Chen, Darshan S Chandrashekar, Sooryanarayana Varambally, Rajeev S Samant, Lalita A Shevde
Host responses to tumor cells include tumor suppressing or promoting mechanisms. We sought to detail the effect of Hedgehog (Hh) pathway inhibition on the composition of the mammary tumor immune portfolio. We hypothesized that Hh signaling mediates a crosstalk between breast cancer cells and macrophages that dictates alternative polarization of macrophages and consequently supports a tumor-promoting microenvironment. We used an immunocompetent, syngeneic mouse mammary cancer model to inhibit Hh signaling with the pharmacological inhibitor, Vismodegib...
2019: Oncoimmunology
https://read.qxmd.com/read/30720181/effects-of-mir-153-on-angiogenesis-in-mcao-rats-through-shh-signaling-pathway
#17
B-X Wang, J-J Xu, J Hu, M-L Hu, J-M Huang, X-D Zhu
OBJECTIVE: Cerebrovascular disease is a disease which has the highest mortality in China. Angiogenesis in the ischemic region after cerebral infarction is closely related to its prognosis. Recent studies found that microRNAs (miRNAs) are involved in the regulation of neovascularization. MicroRNA-153 (MiR-153) has protective effects on the ischemic injury, but its relationship with the Sonic Hedgehog (Shh) signaling pathway is still unclear. This work aimed to investigate the role of miR-153 in angiogenesis of middle cerebral artery occlusion (MCAO) rats through the Shh signaling pathway...
January 2019: European Review for Medical and Pharmacological Sciences
https://read.qxmd.com/read/30720134/triacetyl-resveratrol-upregulates-mirna%C3%A2-200-and-suppresses-the-shh-pathway-in-pancreatic-cancer-a-potential-therapeutic-agent
#18
Junsheng Fu, Anju Shrivastava, Sushant K Shrivastava, Rakesh K Srivastava, Sharmila Shankar
Trans‑3,4',5‑trihydroxystilbene (resveratrol) is a naturally occurring polyphenolic phytoalexin with marked anticancer activities, and is mainly found in grapes, berries and peanuts. However, due to a low bioavailability, it has not progressed to clinical practice for cancer treatment. Therefore, the aims of the present study were to examine the anticancer activities of the resveratrol derivative, triacetyl resveratrol (TCRV), in pancreatic cancer cells. Apoptosis was measured by fluorescence‑activated cell sorting and terminal deoxynucleotidyl transferase (TdT)‑mediated dUTP nick‑end labeling assays...
January 28, 2019: International Journal of Oncology
https://read.qxmd.com/read/30719823/klf2-inhibits-hepatocarcinogenesis-through-negative-regulation-of-the-hedgehog-pathway
#19
JinBo Lin, Huifang Tan, Yingjie Nie, Dongwen Wu, Weiji Zheng, Wensong Lin, Zheng Zhu, Bing Yang, Xiaoliang Chen, Tao Chen
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The most important reason for the occurrence of HCC is HCV or HBV infection. Moreover, genetic factors play an important role in the tumorigenesis of HCC. Here, we demonstrated that Krüppel-like factor2 (KLF2) expression was downregulated in HCC samples compared with adjacent tissues. Additionally, KLF2 was shown to inhibit the growth, migration and colony formation ability of liver cancer cells. Further mechanistic studies revealed that KLF2 can compete with Gli1 for interaction with HDAC1 and restrains Hedgehog signal activation...
February 4, 2019: Cancer Science
https://read.qxmd.com/read/30714153/sonic-hedgehog-pathway-activation-regulates-cervical-cancer-stem-cell-characteristics-during-epithelial-to-mesenchymal-transition
#20
Anuka Sharma, Renaissa De, Shifa Javed, Radhika Srinivasan, Arnab Pal, Shalmoli Bhattacharyya
Resistance to therapy and metastasis remains one of the leading causes of mortality due to cervical cancer despite advances in detection and treatment. The mechanism of epithelial to mesenchymal transition (EMT) provides conceptual explanation to the invasiveness and metastatic spread of cancer but it has not been fully understood in cervical cancer. This study aims to investigate the mechanism by which silencing of E-cadherin gene regulates EMT leading to proliferation, invasion, and chemoresistance of cervical cancer cells through the Hedgehog (Hh) signaling pathway...
February 4, 2019: Journal of Cellular Physiology
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