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https://www.readbyqxmd.com/read/28219952/enthesis-regeneration-a-role-for-gli1-progenitor-cells
#1
Andrea G Schwartz, Leesa M Galatz, Stavros Thomopoulos
The tendon enthesis originates from a specific pool of hedgehog-active Gli1+ progenitor cells that differentiate and produce mineralized fibrocartilage. The current study investigated the regenerative capacity of this cell population by comparing the responses of early postnatal and mature entheses to injury. Lineage tracing studies demonstrated that the original Gli1+ cell population had the capacity to heal immature entheses after injury but this capacity was lost after the cells differentiated into mature fibrochondrocytes...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28213929/exploration-of-the-brn4-regulated-genes-enhancing-adult-hippocampal-neurogenesis-by-rna-sequencing
#2
Jingjing Guo, Xiang Cheng, Lei Zhang, Linmei Wang, Yongxin Mao, Guixiang Tian, Wenhao Xu, Yuhao Wu, Zhi Ma, Jianbing Qin, Meiling Tian, Guohua Jin, Wei Shi, Xinhua Zhang
Adult hippocampal neurogenesis is essential for learning and memory, and its dysfunction is involved in neurodegenerative diseases. However, the molecular mechanisms underlying adult hippocampal neurogenesis are still largely unknown. Our previous studies indicated that the transcription factor Brn4 was upregulated and promoted neuronal differentiation of neural stem cells (NSCs) in the surgically denervated hippocampus in rats. In this study, we use high-throughput RNA sequencing to explore the molecular mechanisms underlying the enhancement of adult hippocampal neurogenesis induced by lentivirus-mediated Brn4 overexpression in vivo...
February 18, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28208838/the-effect-of-metformin-and-gant61-combinations-on-the-radiosensitivity-of-prostate-cancer-cells
#3
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Ruth J Muschel, Karin Haustermans
The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28195165/smoothened-is-a-poor-prognosis-factor-and-a-potential-therapeutic-target-in-glioma
#4
Yiming Tu, Mingshan Niu, Peng Xie, Chenglong Yue, Ning Liu, Zhenglei Qi, Shangfeng Gao, Hongmei Liu, Qiong Shi, Rutong Yu, Xuejiao Liu
Malignant gliomas are associated with a high mortality rate. Thus, there is an urgent need for the development of novel targeted therapeutics. Aberrant Hedgehog signaling has been directly linked to glioma. GDC-0449 is a novel small molecule inhibitor of Hedgehog signaling that blocks the activity of smoothened (Smo). In this study, we evaluated the in vitro and in vivo effects of the smoothened inhibitor GDC-0449 on cell proliferation in human gliomas. We found that high expression of smoothened in glioma is a predictor of short overall survival and poor patient outcome...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28188758/a-role-for-the-hedgehog-effector-gli1-in-mediating-stent-induced-ureteral-smooth-muscle-dysfunction-and-aperistalsis
#5
Claudia Janssen, Ralph Buttyan, Chun Y Seow, Wolfgang Jäger, Dennis Solomon, Ladan Fazli, Ben H Chew, Dirk Lange
OBJECTIVES: To better understand the effects of Double J (JJ) stenting on ureteral physiology and function. MATERIALS AND METHODS: In total, twenty-four pigs (24) were stented cystoscopically unilaterally for 48h, 1, 2, 4 and 7 wks. Controls consisted of un-stented animals (n=4) or the contralateral un-stented ureter in pigs. Ureters were harvested and tested in tissue baths to evaluate their contractility. Ureteral inflammation and expression of Sonic Hedgehog (Shh) and the transcriptional activator Gli1 (the downstream target of active HH signaling) were assessed histologically and by immunohistochemistry, respectively...
February 8, 2017: Urology
https://www.readbyqxmd.com/read/28179296/itraconazole-inhibits-akt-mtor-signaling-and-proliferation-in-endometrial-cancer-cells
#6
Hiroshi Tsubamoto, Kayo Inoue, Kazuko Sakata, Tomoko Ueda, Ryu Takeyama, Hiroaki Shibahara, Takashi Sonoda
BACKGROUND: Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells. MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28167794/gata4-potentiates-second-heart-field-proliferation-and-hedgehog-signaling-for-cardiac-septation
#7
Lun Zhou, Jielin Liu, Menglan Xiang, Patrick Olson, Alexander Guzzetta, Ke Zhang, Ivan P Moskowitz, Linglin Xie
GATA4, an essential cardiogenic transcription factor, provides a model for dominant transcription factor mutations in human disease. Dominant GATA4 mutations cause congenital heart disease (CHD), specifically atrial and atrioventricular septal defects (ASDs and AVSDs). We found that second heart field (SHF)-specific Gata4 heterozygote embryos recapitulated the AVSDs observed in germline Gata4 heterozygote embryos. A proliferation defect of SHF atrial septum progenitors and hypoplasia of the dorsal mesenchymal protrusion, rather than anlage of the atrioventricular septum, were observed in this model...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28167297/loss-of-pin1-suppresses-hedgehog-driven-medulloblastoma-tumorigenesis
#8
Tao Xu, Honglai Zhang, Sung-Soo Park, Sriram Venneti, Rork Kuick, Kimberly Ha, Lowell Evan Michael, Mariarita Santi, Chiyoko Uchida, Takafumi Uchida, Ashok Srinivasan, James M Olson, Andrzej A Dlugosz, Sandra Camelo-Piragua, Jean-François Rual
Medulloblastoma is the most common malignant brain tumor in children. Therapeutic approaches to medulloblastoma (combination of surgery, radiotherapy, and chemotherapy) have led to significant improvements, but these are achieved at a high cost to quality of life. Alternative therapeutic approaches are needed. Genetic mutations leading to the activation of the Hedgehog pathway drive tumorigenesis in ~30% of medulloblastoma. In a yeast two-hybrid proteomic screen, we discovered a novel interaction between GLI1, a key transcription factor for the mediation of Hedgehog signals, and PIN1, a peptidylprolyl cis/trans isomerase that regulates the postphosphorylation fate of its targets...
February 3, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28161934/identification-of-diverse-adenosine-to-inosine-rna-editing-subtypes-in-colorectal-cancer
#9
Si-Hyun Lee, Hwang-Phill Kim, Jun-Kyu Kang, Sang-Hyun Song, Sae-Won Han, Tae-You Kim
Purpose: RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-Inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer. Therefore, this study was conducted to identify diverse RNA editing in colorectal cancer. Materials and Methods: We compared transcriptome data of 39 colorectal cancer (CRC) samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions...
January 25, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28160546/expression-and-role-of-anion-exchanger-1-in-esophageal-squamous-cell-carcinoma
#10
Atsushi Shiozaki, Michihiro Kudou, Daisuke Ichikawa, Hiroki Shimizu, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Yoshinori Marunaka, Eigo Otsuji
Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159470/hedgehog-pathway-plays-a-vital-role-in-hiv-induced-epithelial-mesenchymal-transition-of-podocyte
#11
Xiqian Lan, Hongxiu Wen, Kang Cheng, Andrei Plagov, Seyedeh Shadafarin Marashi Shoshtari, Ashwani Malhotra, Pravin C Singhal
HIV-associated nephropathy (HIVAN) is characterized by heavy proteinuria, rapidly progressive renal failure, and distinct morphological features in the kidney. HIV-induced epithelial-mesenchymal transition (EMT) is critically important for the progression of kidney injury. In this study, we tested the role of hedgehog pathway in the HIV-induced EMT and fibrosis of kidney. We used the Tg26 mice, the abundantly used HIVAN mouse model, to investigate the activation of hedgehog pathway by HIV. Western blotting and real time PCR results showed that renal tissue expression of hedgehog pathway related molecules, including hedgehog homologous (Shh, Ihh, Dhh), PTCH, and Gli1, were increased in HIVAN (Tg26) mice; while immunofluorescent staining displayed localization PTCH expression in podocytes...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28148565/pirfenidone-exerts-antifibrotic-effects-through-inhibition-of-gli-transcription-factors
#12
Miroslava Didiasova, Rajeev Singh, Jochen Wilhelm, Grazyna Kwapiszewska, Lukasz Wujak, Dariusz Zakrzewicz, Liliana Schaefer, Philipp Markart, Werner Seeger, Matthias Lauth, Malgorzata Wygrecka
Pirfenidone is an antifibrotic drug, recently approved for the treatment of patients suffering from idiopathic pulmonary fibrosis (IPF). Although pirfenidone exhibits anti-inflammatory, antioxidant, and antifibrotic properties, the molecular mechanism underlying its protective effects remains unknown. Here, we link pirfenidone action with the regulation of the profibrotic hedgehog (Hh) signaling pathway. We demonstrate that pirfenidone selectively destabilizes the glioma-associated oncogene homolog (GLI)2 protein, the primary activator of Hh-mediated gene transcription...
February 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28148279/aberrant-activation-of-hedgehog-signaling-promotes-cell-proliferation-via-the-transcriptional-activation-of-forkhead-box-m1-in-colorectal-cancer-cells
#13
DeJie Wang, Guohui Hu, Ying Du, Cheng Zhang, Quqin Lu, Nonghua Lv, Shiwen Luo
BACKGROUND: Recent evidence suggests that the aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas, including colorectal cancer (CRC). Forkhead box M1 (FoxM1) controls the expression of a number of cell cycle regulatory proteins, and FoxM1 expression is elevated in a broad range of human malignancies, which suggests that it plays a crucial role in tumorigenesis. However, the mechanisms underlying FoxM1 expression are not fully understood...
February 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28144905/anti-cell-growth-and-anti-cancer-stem-cell-activities-of-the-non-canonical-hedgehog-inhibitor-gant61-in-triple-negative-breast-cancer-cells
#14
Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriya, Junichi Kurebayashi
BACKGROUND: Triple-negative breast cancer (TNBC) exhibits biologically aggressive behavior and has a poor prognosis. Novel molecular targeting agents are needed to control TNBC. Recent studies revealed that the non-canonical hedgehog (Hh) signaling pathway plays important roles in the regulation of cancer stem cells (CSCs) in breast cancer. Therefore, the anti-cell growth and anti-CSC effects of the non-canonical Hh inhibitor GANT61 were investigated in TNBC cells. METHODS: The effects of GANT61 on cell growth, cell cycle progression, apoptosis, and the proportion of CSCs were investigated in three TNBC cell lines...
January 31, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28143780/msi2-maintains-quiescent-state-of-hair-follicle-stem-cells-by-directly-repressing-the-hh-signaling-pathway
#15
Xianghui Ma, Yuhua Tian, Yongli Song, Jianyun Shi, Jiuzhi Xu, Kai Xiong, Jia Li, Wenjie Xu, Yiqiang Zhao, Jianwei Shuai, Lei Chen, Maksim V Plikus, Christopher Lengner, Fazheng Ren, Lixiang Xue, Zhengquan Yu
Hair follicles (HFs) undergo precisely regulated cycles of active regeneration consisting of (anagen), involution (catagen), and relative quiescence (telogen) phases. HF stem cells (HFSCs) play important roles in regenerative cycling. Elucidating mechanisms that governs HFSC behavior can help uncover the underlying principles of hair development, hair growth disorders and skin cancers. RNA-binding proteins of the Musashi (Msi) have been implicated in the biology of different stem cell types, yet they have not been studied in HFSCs...
January 28, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28134963/gli1-expression-in-human-epiretinal-membranes
#16
Sohee Jeon, Jiwon Baek, Won Ki Lee
Purpose: We evaluate the expression of Gli1 in human epiretinal membranes (ERM) and correlate this with clinical data. Methods: We prospectively recruited patients with ERM. A total of 33 human ERM specimens were immunolabeled with anti-Gli1 antibody and the number of total cells/hyperfield (HF), Gli1(+) cells/HF, and the percentage of Gli1(+) cells/total cells were calculated. We evaluated the interrelationship of cellular properties and clinical findings, such as presence of diabetic retinopathy (DR), retinal breaks, intraocular inflammation, central foveal thickness, maximal retinal thickness, retinal contraction, lamellar holes, pseudoholes, the attenuation or absence of an inner segment/outer segment (IS/OS) junction/external limiting membrane (ELM), cystic changes, and paravascular inner retinal defects...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28123507/inhibition-of-the-cyclind1-promoter-in-response-to-sonic-hedgehog-signaling-pathway-transduction-is-mediated-by-gli1
#17
Zhongxiao Lin, Hansong Sheng, Chaoguo You, Ming Cai, Yiping Zhang, Li Sheng Yu, Xiaoming Yu, Jian Lin, Nu Zhang
Medulloblastoma (MB) is the most common malignant tumor of the central nervous system in children. Accumulating evidence suggests a major role for the activation of the sonic hedgehog (SHH) signaling pathway in the development of MB cells; however, the mechanisms underlying the effect of this pathway on tumor survival and growth remain poorly understood. The Gli family zinc finger 1 (Gli1) transcription factor is considered as a mediator of the SHH signaling pathway in MB cells. Therefore, the present study investigated whether the SHH signaling pathway promotes the apoptosis of MB cells via downregulation of Gli1...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28112165/loss-of-merlin-induces-metabolomic-adaptation-that-engages-dependence-on-hedgehog-signaling
#18
Shamik Das, William P Jackson, Jeevan K Prasain, Ann Hanna, Sarah K Bailey, J Allan Tucker, Sejong Bae, Landon S Wilson, Rajeev S Samant, Stephen Barnes, Lalita A Shevde
The tumor suppressor protein Merlin is proteasomally degraded in breast cancer. We undertook an untargeted metabolomics approach to discern the global metabolomics profile impacted by Merlin in breast cancer cells. We discerned specific changes in glutathione metabolites that uncovered novel facets of Merlin in impacting the cancer cell metabolome. Concordantly, Merlin loss increased oxidative stress causing aberrant activation of Hedgehog signaling. Abrogation of GLI-mediated transcription activity compromised the aggressive phenotype of Merlin-deficient cells indicating a clear dependence of cells on Hedgehog signaling...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098170/targeting-the-pi3k-akt-pathway-via-gli1-inhibition-enhanced-the-drug-sensitivity-of-acute-myeloid-leukemia-cells
#19
Hui Liang, Qi-Li Zheng, Peng Fang, Jian Zhang, Tuo Zhang, Wei Liu, Min Guo, Christopher L Robinson, Shui-Bing Chen, Xiao-Ping Chen, Fang-Ping Chen, Hui Zeng
Combination targeted therapy is commonly used to treat acute myeloid leukemia (AML) patients, particularly in refractory/relapse (RR) population. However, concerns have been raised regarding the safety and patient tolerance of combination chemotherapy. It is critical to choose the appropriate treatment for precision therapy. We performed genome-wide RNA profiling using RNA-Seq to compare the RR group and the complete remission (CR) group (a total of 42 adult AML patients). The Hedgehog (Hh) and PI3K/AKT pathways were upregulated in the RR population, which was further confirmed by western blot and/or qPCR...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069799/ikbke-is-required-during-kras-induced-pancreatic-tumorigenesis
#20
Mihir Rajurkar, Kyvan Dang, Maite G Fernandez-Barrena, Xiangfan Liu, Martin E Fernandez-Zapico, Brian C Lewis, Junhao Mao
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies lacking effective therapeutic strategies. Here, we show that the noncanonical IκB-related kinase, IKBKE, is a critical oncogenic effector during KRAS-induced pancreatic transformation. Loss of IKBKE inhibits the initiation and progression of pancreatic tumors in mice carrying pancreatic-specific KRAS activation. Mechanistically, we demonstrate that this protumoral effect of IKBKE involves the activation of GLI1 and AKT signaling and is independent of the levels of activity of the NF-κB pathway...
January 15, 2017: Cancer Research
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