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SKI gene and cancer

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https://www.readbyqxmd.com/read/29892481/transcriptional-cofactors-ski-and-snon-are-major-regulators-of-the-tgf-%C3%AE-smad-signaling-pathway-in-health-and-disease
#1
Angeles C Tecalco-Cruz, Diana G Ríos-López, Genaro Vázquez-Victorio, Reyna E Rosales-Alvarez, Marina Macías-Silva
The transforming growth factor-β (TGF-β) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-β signaling pathway outcome relies on the control of the spatial and temporal expression of >500 genes, which depend on the functions of the Smad protein along with those of diverse modulators of this signaling pathway, such as transcriptional factors and cofactors. Ski (Sloan-Kettering Institute) and SnoN (Ski novel) are Smad-interacting proteins that negatively regulate the TGF-β signaling pathway by disrupting the formation of R-Smad/Smad4 complexes, as well as by inhibiting Smad association with the p300/CBP coactivators...
2018: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29799477/deregulation-of-negative-controls-on-tgf-%C3%AE-1-signaling-in-tumor-progression
#2
REVIEW
Jiaqi Tang, Cody C Gifford, Rohan Samarakoon, Paul J Higgins
The multi-functional cytokine transforming growth factor-β1 (TGF-β1) has growth inhibitory and anti-inflammatory roles during homeostasis and the early stages of cancer. Aberrant TGF-β activation in the late-stages of tumorigenesis, however, promotes development of aggressive growth characteristics and metastatic spread. Given the critical importance of this growth factor in fibrotic and neoplastic disorders, the TGF-β1 network is subject to extensive, multi-level negative controls that impact receptor function, mothers against decapentaplegic homolog 2/3 (SMAD2/3) activation, intracellular signal bifurcation into canonical and non-canonical pathways and target gene promotor engagement...
May 25, 2018: Cancers
https://www.readbyqxmd.com/read/29588413/hydrophobic-patches-on-smad2-and-smad3-determine-selective-binding-to-cofactors
#3
Ken-Ichi Miyazono, Saho Moriwaki, Tomoko Ito, Akira Kurisaki, Makoto Asashima, Masaru Tanokura
The transforming growth factor-β (TGF-β) superfamily of cytokines regulates various biological processes, including cell proliferation, immune responses, autophagy, and senescence. Dysregulation of TGF-β signaling causes various diseases, such as cancer and fibrosis. SMAD2 and SMAD3 are core transcription factors involved in TGF-β signaling, and they form heterotrimeric complexes with SMAD4 (SMAD2-SMAD2-SMAD4, SMAD3-SMAD3-SMAD4, and SMAD2-SMAD3-SMAD4) in response to TGF-β signaling. These heterotrimeric complexes interact with cofactors to control the expression of TGF-β-dependent genes...
March 27, 2018: Science Signaling
https://www.readbyqxmd.com/read/29510895/effect-of-abcg2-oct1-and-abcb1-mdr1-gene-expression-on-treatment-free-remission-in-a-euro-ski-subtrial
#4
Sébastien Rinaldetti, Markus Pfirrmann, Kirsi Manz, Joelle Guilhot, Christian Dietz, Panayiotidis Panagiotidis, Birgit Spiess, Wolfgang Seifarth, Alice Fabarius, Martin Müller, Maria Pagoni, Maria Dimou, Jolanta Dengler, Cornelius F Waller, Tim H Brümmendorf, Regina Herbst, Andreas Burchert, Carsten Janβen, Maria Elisabeth Goebeler, Philipp J Jost, Stefan Hanzel, Philippe Schafhausen, Gabriele Prange-Krex, Thomas Illmer, Viktor Janzen, Martine Klausmann, Robert Eckert, Gerd Büschel, Alexander Kiani, Wolf-Karsten Hofmann, François-Xavier Mahon, Susanne Saussele
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. MATERIALS AND METHODS: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29358619/novel-therapeutic-strategy-for-cervical-cancer-harboring-fgfr3-tacc3-fusions
#5
Ryo Tamura, Kosuke Yoshihara, Tetsuya Saito, Ryosuke Ishimura, Juan Emmanuel Martínez-Ledesma, Hu Xin, Tatsuya Ishiguro, Yutaro Mori, Kaoru Yamawaki, Kazuaki Suda, Seiya Sato, Hiroaki Itamochi, Teiichi Motoyama, Yoichi Aoki, Shujiro Okuda, Cristine R Casingal, Hirofumi Nakaoka, Ituro Inoue, Roel G W Verhaak, Masaaki Komatsu, Takayuki Enomoto
We previously found that therapeutic targetable fusions are detected across various cancers. To identify therapeutic targetable fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cervical cancer samples. We detected 445 high confidence fusion transcripts and identified four samples that harbored FGFR3-TACC3 fusion as an attractive therapeutic target. The frequency of FGFR3-TACC3-fusion-positive cervical cancer is also 1...
January 23, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29191063/changes-in-dna-methylation-induced-by-multi-walled-carbon-nanotube-exposure-in-the-workplace
#6
Manosij Ghosh, Deniz Öner, Katrien Poels, Ali M Tabish, Jelle Vlaanderen, Anjoeka Pronk, Eelco Kuijpers, Qing Lan, Roel Vermeulen, Bram Bekaert, Peter Hm Hoet, Lode Godderis
This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th cytosine residues using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. Sequence-specific methylation of LINE1 retrotransposable element 1 (L1RE1) elements, and promoter regions of functionally important genes associated with epigenetic regulation [DNA methyltransferase-1 (DNMT1) and histone deacetylase 4 (HDAC4)], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator of histone transcription/ATM serine/threonine kinase (NPAT/ATM)], and a potential transforming growth factor beta (TGF-β) repressor [SKI proto-oncogene (SKI)] were studied using bisulfite pyrosequencing...
November 2017: Nanotoxicology
https://www.readbyqxmd.com/read/29118270/upregulation-of-pir-gene-expression-induced-by-human-papillomavirus-e6-and-e7-in-epithelial-oral-and-cervical-cells
#7
Diego Carrillo, Juan P Muñoz, Hernán Huerta, Gabriel Leal, Alejandro Corvalán, Oscar León, Gloria M Calaf, Ulises Urzúa, Enrique Boccardo, Julio C Tapia, Francisco Aguayo
The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells...
November 2017: Open Biology
https://www.readbyqxmd.com/read/28681918/microrna-137-is-negatively-associated-with-clinical-outcome-and-regulates-tumor-development-through-ezh2-in-cervical-cancer
#8
Huimin Zhang, Ting Yan, Zhijun Liu, Jun Wang, Yu Lu, Donglin Li, Wentong Liang
We intend to evaluate the expression, clinical relevance, and functional role of microRNA-137 (miR-137) in human cervical cancer (CC). MiR-137 expressions were assessed by qPCR in CC cell lines and human CC tumors. The correlation between endogenous miR-137 expression and CC patients' postoperative overall survival was examined statistically. CC cell lines, Ca-Ski, and SiHa cells were transduced with lentivirus to ectopically upregulate endogenous miR-137 expressions. Possible inhibitory effects of miR-137 upregulation on CC in vitro proliferation and migration, as well as in vivo transplantation were evaluated...
January 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28577497/microrna-505-predicts-prognosis-and-acts-as-tumor-inhibitor-in-cervical-carcinoma-with-inverse-association-with-fzd4
#9
Chunhua Ma, Baomei Xu, Sulaiya Husaiyin, Lin Wang, Kunduozi Wusainahong, Jin Ma, Kaichun Zhu, Mayinuer Niyazi
PURPOSE: We investigated the expression and mechanisms of microRNA-505 (miR-505) and its downstream target gene Frizzled-4 (FZD4) in cervical cancer. METHODS: miR-505 expression was evaluated by qRT-PCR in cervical cancer cell lines and human carcinomas. Cancer patients' clinicopathological factors and survival were analyzed based on their tumorous miR-505 levels. Ca-Ski and HeLa cells were transduced with lentivirus to upregulate or downregulate miR-505. Their impacts on cervical cancer were evaluated by in vitro proliferation, invasion and in vivo tumorigenicity assays, respectively...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28521287/5azadc-treatment-upregulates-mir-375-level-and-represses-hpv16-e6-expression
#10
Adrien Morel, Aurélie Baguet, Jérôme Perrard, Caroline Demeret, Elise Jacquin, David Guenat, Christiane Mougin, Jean-Luc Prétet
High-risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is the most oncogenic genotype. Immortalization and transformation of infected cells requires the overexpression of the two viral oncoproteins E6 and E7 following HPV DNA integration into the host cell genome. Integration often leads to the loss of the E2 open reading frame and the corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes to the regulation of E6/E7 expression...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487767/inducement-of-apoptosis-by-cucurbitacin-e-a-tetracyclic-triterpenes-through-death-receptor-5-in-human-cervical-cancer-cell-lines
#11
Ya-Min Cheng, Ching-Ju Shen, Chi-Chang Chang, Cheng-Yang Chou, Ching-Chou Tsai, Yi-Chiang Hsu
Cervical cancer is the most common malignancy in women, for which conization or hysterectomy are the main therapy. Curcubitacin E (Cu E) is a natural compound-based drug which from the Guadi (climbing stem of Cucumic melo L). Previously shown to be an anti-tumor as well as a potent chemopreventive agent against several types of tumors. The present study, investigated anti-proliferation and apoptosis induced by Cu E in cervical cancer cell lines (HeLa and Ca Ski). The results indicate that the cytotoxicity is associated with accumulation in apoptosis but not necrosis...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28398634/ski-regulates-smads-and-taz-signaling-to-suppress-lung-cancer-progression
#12
Mian Xie, Xiaojun Wu, Jinjun Zhang, Jiexia Zhang, Xiangxiang Li
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, displays both pro- and anti-oncogenic activities in human cancer. The mechanisms underlying these conflicting observations have not been fully understood. Herein, we investigated the mechanism underlying the tumor suppressor activity of Ski. To investigate the effect of Ski re-activation on TGF-β and Hippo/TAZ pathway, we measured its effect on the endogenous Smad target genes (PAI-1 and P15(INK4B) ) and TAZ target gene CTGF. The results revealed that Ski exerted its inhibitory activity in TGF-β1/Smad signaling pathway...
October 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28165392/sphingosine-kinase-1-involves-the-inhibitory-action-of-hif-1%C3%AE-by-chlorogenic-acid-in-hypoxic-du145-cells
#13
Myoung-Sun Lee, Seon-Ok Lee, Kyu-Ri Kim, Hyo-Jeong Lee
Hypoxia enhances cancer development in a solid tumor. Hypoxia-inducible factor-1 α (HIF-1α) is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor that regulates tumor. HIF-1α regulates several target genes involved in many aspects of cancer progression, including angiogenesis, metastasis, anti-apoptosis and cell proliferation as well as imparts resistance to cancer treatment. In this study, we assessed Crataegus Pinnatifida Bunge var. typical Schneider ethanol extract (CPE) for its anti-cancer effects in hypoxia-induced DU145 human prostate cancer cell line...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28115165/repression-of-smad3-by-stat3-and-c-ski-snon-induces-gefitinib-resistance-in-lung-adenocarcinoma
#14
Yojiro Makino, Jeong-Hwan Yoon, Eunjin Bae, Mitsuyasu Kato, Keiji Miyazawa, Tatsuo Ohira, Norihiko Ikeda, Masahiko Kuroda, Mizuko Mamura
Cancer-associated inflammation develops resistance to the epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancers (NSCLCs) harboring oncogenic EGFR mutations. Stat3-mediated interleukin (IL)-6 signaling and Smad-mediated transforming growth factor-β (TGF-β) signaling pathways play crucial regulatory roles in cancer-associated inflammation. However, mechanisms how these pathways regulate sensitivity and resistance to EGFR-TKI in NSCLCs remain largely undetermined...
March 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27909446/functional-toxicogenomic-profiling-expands-insight-into-modulators-of-formaldehyde-toxicity-in-yeast
#15
Matthew North, Brandon D Gaytán, Carlos Romero, Vanessa Y De La Rosa, Alex Loguinov, Martyn T Smith, Luoping Zhang, Chris D Vulpe
Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s) of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27137215/identification-of-key-regulators-of-pancreatic-cancer-progression-through-multidimensional-systems-level-analysis
#16
Deepa Rajamani, Manoj K Bhasin
BACKGROUND: Pancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression...
May 3, 2016: Genome Medicine
https://www.readbyqxmd.com/read/26944438/sphk1-inhibitor-ski-ii-inhibits-the-proliferation-of-human-hepatoma-hepg2-cells-via-the-wnt5a-%C3%AE-catenin-signaling-pathway
#17
Hong Liu, Cai-Xia Zhang, Yan Ma, Hong-Wei He, Jia-Ping Wang, Rong-Guang Shao
AIM: Sphingosine 1-phosphate (S1P) promotes cell growth, proliferation and survival. Sphingosine kinase 1 (SphK1), which converts sphingosine to S1P, is a key promoter in cancer. We previously found that the SphK1 inhibitor II (SKI II), suppresses the cell growth and induces apoptosis in human hepatoma HepG2 cells. However, the precise regulatory mechanism and signaling pathway on SKI II inhibiting tumor growth remains unknown. MAIN METHODS: The expressions of β-catenin and related molecules of Wnt/β-catenin signal were detected by western blot in HepG2 cells...
April 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/26766902/microrna-125a-5p-modulates-human-cervical-carcinoma-proliferation-and-migration-by-targeting-abl2
#18
Xian Qin, Yajun Wan, Saiying Wang, Min Xue
BACKGROUND: In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p) in human cervical carcinoma. METHODS: The gene expressions of miR-125a-5p in seven cervical carcinoma cell lines and 12 human cervical carcinoma samples were evaluated by quantitative real-time reverse transcription polymerase chain reaction. Ca-Ski and HeLa cells were transduced with lentivirus carrying miR-125a-5p mimics, and the effects of lentivirus-induced miR-125a-5p upregulation on cervical carcinoma proliferation and migration were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and transwell assays, respectively...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/26293898/the-anti-ovarian-cancer-activity-by-wye-132-a-mtorc1-2-dual-inhibitor
#19
Dan Zhang, Hexia Xia, Wei Zhang, Bo Fang
Epithelial ovarian cancer is the most common and lethal gynecological cancer in USA and around the world, causing major mortality annually. In the current study, we investigated the potential anti-ovarian cancer activity of WYE-132, a mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor. Our results showed that WYE-132 potently inhibited proliferation of primary and established human ovarian cancer cells. Meanwhile, WYE-132 induced caspase-dependent apoptosis in ovarian cancer cells. At the molecular level, WYE-132 blocked mTORC1/2 activation and inhibited expression of mTOR-regulated genes (cyclin D1 and hypoxia-inducible factor 1α)...
January 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26208712/l-and-d-lactate-enhance-dna-repair-and-modulate-the-resistance-of-cervical-carcinoma-cells-to-anticancer-drugs-via-histone-deacetylase-inhibition-and-hydroxycarboxylic-acid-receptor-1-activation
#20
Waldemar Wagner, Wojciech M Ciszewski, Katarzyna D Kania
BACKGROUND: The consideration of lactate as an active metabolite is a newly emerging and attractive concept. Recently, lactate has been reported to regulate gene transcription via the inhibition of histone deacetylases (HDACs) and survival of cancer cells via hydroxycarboxylic acid receptor 1 (HCAR1). This study examined the role of L- and D-lactate in the DNA damage response in cervical cancer cells. METHODS: Three cervical cancer cell lines were examined: HeLa, Ca Ski and C33A...
2015: Cell Communication and Signaling: CCS
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