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https://www.readbyqxmd.com/read/28635133/critical-role-of-glioma-associated-oncogene-homolog-1-in-maintaining-invasive-and-mesenchymal-like-properties-of-melanoma-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28576771/bmp-signaling-orchestrates-a-transcriptional-network-to-control-the-fate-of-mesenchymal-stem-cells-in-mice
#8
Jifan Feng, Junjun Jing, Jingyuan Li, Hu Zhao, Vasu Punj, Tingwei Zhang, Jian Xu, Yang Chai
Signaling pathways are used reiteratively in different developmental processes yet produce distinct cell fates through specific downstream transcription factors. In this study, we used tooth root development as a model to investigate how the BMP signaling pathway regulates transcriptional complexes to direct the fate determination of multipotent mesenchymal stem cells (MSCs). We first identified the MSC population supporting mouse molar root growth as Gli1+ cells. Using a Gli1-mediated transgenic animal model, our results provide the first in vivo evidence that BMP signaling activity is required for the odontogenic differentiation of MSCs...
June 2, 2017: Development
https://www.readbyqxmd.com/read/28576690/complement-component-c3ar-constitutes-a-novel-regulator-for-chick-eye-morphogenesis
#9
Erika Grajales-Esquivel, Agustin Luz-Madrigal, Jeffrey Bierly, Tracy Haynes, Edimara S Reis, Zeyu Han, Christian Gutierrez, Zachary McKinney, Apostolia Tzekou, John D Lambris, Panagiotis A Tsonis, Katia Del Rio-Tsonis
Complement components have been implicated in a wide variety of functions including neurogenesis, proliferation, cell migration, differentiation, cancer, and more recently early development and regeneration. Following our initial observations indicating that C3a/C3aR signaling induces chick retina regeneration, we analyzed its role in chick eye morphogenesis. During eye development, the optic vesicle (OV) invaginates to generate a bilayer optic cup (OC) that gives rise to the retinal pigmented epithelium (RPE) and neural retina...
May 30, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28575684/gli-fully-halting-the-progression-of-fibrosis
#10
Christian F Guerrero-Juarez, Maksim V Plikus
Activating triggers, selective markers, and the residual regenerative potential of scar-forming myofibroblasts are largely determined by their origin. In this issue of Cell Stem Cell, Schneider et al. report that bone marrow myofibroblasts derive from Gli1(+) mesenchymal stromal cells and that a Gli inhibitor targets them for elimination in mice and humans, ameliorating fibrosis.
June 1, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28575066/combined-application-of-arsenic-trioxide-and-lithium-chloride-augments-viability-reduction-and-apoptosis-induction-in-human-rhabdomyosarcoma-cell-lines
#11
Sabine B Schleicher, Julian J Zaborski, Rosa Riester, Natascha Zenkner, Rupert Handgretinger, Torsten Kluba, Frank Traub, Karen A Boehme
Rhabdomyosarcomas (RMS) are the most prevalent soft tissue sarcomas affecting children and adolescents. Despite intensive treatment consisting of multimodal chemotherapy and surgery RMS patients diagnosed with metastatic disease expect long term survival rates of only 20%. Often multidrug resistance arises upon initial response emphasizing the need for new therapeutic drugs to improve treatment efficiency. Previously, we demonstrated the efficacy of the FDA approved drug arsenic trioxide (ATO) specifically inhibiting viability and clonal growth as well as inducing cell death in human RMS cell lines of different subtypes...
2017: PloS One
https://www.readbyqxmd.com/read/28573530/mecp2-regulates-ptch1-expression-through-dna-methylation-in-rheumatoid-arthritis
#12
Zheng-Hao Sun, Yan-Hui Liu, Jun-da Liu, Dan-Dan Xu, Xiao-Feng Li, Xiao-Ming Meng, Tao-Tao Ma, Cheng Huang, Jun Li
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, in which pathogenesis is not clear. Many research demonstrated that fibroblast-like synoviocytes (FLSs) play a key role in RA pathogenesis, join in the cartilage injury and hyperplasia of the synovium, and contribute to the release of inflammatory cytokines. We used adjuvant arthritis (AA) rats as RA animal models. The methyl-CpG-binding protein 2 (MeCP2) enables the suppressed chromatin structure to be selectively detected in AA FLSs. Overexpression of this protein leads to an increase of integral methylation levels...
June 1, 2017: Inflammation
https://www.readbyqxmd.com/read/28566426/a-new-therapeutic-target-for-myelofibrosis-is-cause-for-gli
#13
Brian A Jonas
Myeloproliferative neoplasm cells recruit Gli1 positive mesenchymal stromal cells to transdifferentiate into fibrosis-causing myofibroblasts, a process that can be inhibited by a Gli inhibitor.
May 31, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28565875/smoothened-antagonist-gdc-0449-vismodegib-inhibits-proliferation-and-triggers-apoptosis-in-colon-cancer-cell-lines
#14
Chuanqing Wu, Shaobo Hu, Ji Cheng, Guobin Wang, Kaixiong Tao
The sonic hedgehog (Shh) pathway has been proven to be involved in embryonic development and cancer growth. GDC-0449, an antagonist of the hedgehog signaling receptor Smoothened (Smo), was recently approved by the US Food and Drug Administration as a prescription for skin basal cell carcinoma. However, the efficacy of GDC-0449 in the treatment of colon cancer and other malignancies, such as basal cell carcinoma and pancreatic cancer, has remained to be proven. The present study assessed the effect of GDC-0449 on the colon cancer cell lines Caco-2 and Ht-29...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28562331/dual-degradation-signals-destruct-gli1-ampk-inhibits-gli1-through-%C3%AE-trcp-mediated-proteasome-degradation
#15
Rui Zhang, Sherri Y Huang, Kay Ka-Wai Li, Yen-Hsing Li, Wei-Hsuan Hsu, Guang Jun Zhang, Chun-Ju Chang, Jer-Yen Yang
Overexpression of the GLI1 gene has frequently been found in various cancer types, particularly in brain tumors, in which aberrant GLI1 induction promotes cancer cell growth. Therefore, identifying the molecular players controlling GLI1 expression is of clinical importance. Previously, we reported that AMPK directly phosphorylated and destabilized GLI1, resulting in the suppression of the Hedgehog signaling pathway. The current study not only demonstrates that AMPK inhibits GLI1 nuclear localization, but further reveals that β-TrCP plays an essential role in AMPK-induced GLI1 degradation...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28556364/phase-i-study-of-glasdegib-pf-04449913-an-oral-smoothened-inhibitor-in-japanese-patients-with-select-hematologic-malignancies
#16
Yosuke Minami, Hironobu Minami, Toshihiro Miyamoto, Goichi Yoshimoto, Yukio Kobayashi, Wataru Munakata, Yasushi Onishi, Masahiro Kobayashi, Mari Ikuta, Geoffrey Chan, Adrian Woolfson, Chiho Ono, Mohammed Naveed Shaik, Yosuke Fujii, Xianxian Zheng, Tomoki Naoe
The hedgehog signaling pathway regulates multiple morphogenetic processes during embryogenesis. Aberrant activation of the hedgehog pathway signal transduction in adult tissues is associated with the pathogenesis of hematologic malignancies and solid tumors. We report findings from an open-label, multicenter phase I trial of the selective, small-molecule hedgehog signaling inhibitor glasdegib (PF-04449913) in Japanese patients with select advanced hematologic malignancies. Glasdegib was administered as once-daily oral doses (25, 50, and 100 mg) in 28-day cycles after a lead-in dose on Day -5...
May 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28551328/association-of-expression-of-the-hedgehog-signal-with-merkel-cell-polyomavirus-infection-and-prognosis-of-merkel-cell-carcinoma
#17
Teruyuki Kuromi, Michiko Matsushita, Takeshi Iwasaki, Daisuke Nonaka, Satoshi Kuwamoto, Keiko Nagata, Masako Kato, Gen Akizuki, Yukisato Kitamura, Kazuhiko Hayashi
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. 29 MCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28548041/foxr2-promotes-the-proliferation-invasion-and-epithelial-mesenchymal-transition-in-human-colorectal-cancer-cells
#18
Sheng-Qiang Lu, Yan Qiu, Wei-Jie Dai, Xiao-Yu Zhang
Forkhead box R2 (FOXR2), a member of the FOX gene family, has not been very well investigated for its role in cancer. A recent study has shown that FOXR2 is highly expressed in breast cancer samples and is associated with poor prognosis. In addition, FOXR2 was identified as an oncogene in medulloblastoma. Nevertheless, whether FOXR2 plays a role in colorectal cancer (CRC) remains unclear. In the present study, we conducted several in vitro and in vivo studies to investigate the expression and effect of FOXR2 in CRC...
May 24, 2017: Oncology Research
https://www.readbyqxmd.com/read/28547659/quiescent-adult-stem-cells-in-murine-teeth-are-regulated-by-shh-signaling
#19
Yuko Ishikawa, Mitsushiro Nakatomi, Hiroko Ida-Yonemochi, Hayato Ohshima
The mechanisms regulating the maintenance of quiescent adult stem cells in teeth remain to be fully elucidated. Our aim is to clarify the relationship between BrdU label-retaining cells (LRCs) and sonic hedgehog (Shh) signaling in murine teeth. After prenatal BrdU labeling, mouse pups were analyzed during postnatal day 1 (P1) to week 5 (P5W). Paraffin sections were processed for immunohistochemistry for BrdU, Sox2, Gli1, Shh, Patched1 (Ptch1) and Ki67 and for in situ hybridization for Shh and Ptch1. Dense LRCs, Gli1-(+) cells and Ptch1-(+) cells were co-localized in the outer enamel epithelium of the apical bud and apical dental papilla of incisors...
May 26, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28537914/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#20
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
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