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https://www.readbyqxmd.com/read/29240942/overexpression-of-pdr16-confers-resistance-to-complex-sphingolipid-biosynthesis-inhibitor-aureobasidina-in-yeast-saccharomyces-cerevisiae
#1
Yuka Katsuki, Yutaro Yamaguchi, Motohiro Tani
Sphingolipids are essential for normal cell growth of yeast Saccharomyces cerevisiae. AureobasidinA (AbA), an antifungal drug, inhibits Aur1, an enzyme catalysing the synthesis of inositolphosphorylceramide, and induces a strong growth defect in yeast. In this study, we screened for multicopy suppressor genes that confer resistance to AbA, and identified PDR16. In addition, it was found that PDR17, a paralog of PDR16, also functions as a multicopy suppressor. Pdr16 and Pdr17 belong to a family of phosphatidylinositol transfer proteins; however, cells overexpressing the other members of the family hardly exhibited resistance to AbA...
December 12, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29240449/mir-19-5p-enhances-tumorigenesis-in-human-colorectal-cancer-cells-by-targeting-tspyl5
#2
Chao Huang, Hesheng Luo
The cancer suppressor gene, testis-specific protein Y-encoded-like 5 (TSPYL5), has been implicated in various cancers, including colorectal cancer (CRC). In this study, we investigated the role of TSPYL5 in the development of CRC in vitro. First, we used bioinformatics to predict the binding target of TSPYL5, and found that the microRNA, miR-19-5p, bound to the 3' untranslated region (UTR) of TSPYL5. This interaction was further validated by the dual-luciferase assay. Second, we found that overexpressed TSPYL5 enhanced apoptosis in HT29 cells and reduced cell proliferation, reduced cell migration/invasion, and most of the cells accumulated in the G0/G1 phase of the cell cycle...
December 14, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29239688/compromising-asymmetric-stem-cell-division-in-drosophila-central-brain-revisiting-the-connections-with-tumorigenesis
#3
Ana Carmena
Asymmetric cell division (ACD) is an essential process during development for generating cell diversity. In addition, a more recent connection between ACD, cancer and stem cell biology has opened novel and highly intriguing venues in the field. This connection between compromised ACD and tumorigenesis was first demonstrated using Drosophila neural stem cells (neuroblasts, NBs) more than a decade ago and, over the past years, it has also been established in vertebrate stem cells. Here, focusing on Drosophila larval brain NBs, and in light of results recently obtained in our lab, we revisit this connection emphasizing two main aspects: 1) the differences in tumor suppressor activity of different ACD regulators and 2) the potential relevance of environment and temporal window frame for compromised ACD-dependent induction of tumor-like overgrowth...
December 14, 2017: Fly
https://www.readbyqxmd.com/read/29239144/smg-1-inhibition-by-mir-192-215-causes-epithelial-mesenchymal-transition-in-gastric-carcinogenesis-via-activation-of-wnt-signaling
#4
Xiaojing Zhang, Yin Peng, Yong Huang, Mengting Yang, Ruibin Yan, Yanqiu Zhao, Yulan Cheng, Xi Liu, Shiqi Deng, Xianling Feng, Huijuan Lin, Huimin Yu, Si Chen, Zhenfu Zhao, Shanni Li, Kuan Li, Liang Wang, Yanjie Wei, Zhendan He, Xinmin Fan, Stephen J Meltzer, Song Li, Zhe Jin
SMG-1,a member of the phosphoinositide kinase-like kinase family, functioned as a tumor suppressor gene. However, the role of SMG-1 in GC remain uncharacterized. In this study, regulation of SMG-1 by miR-192 and-215, along with the biological effects of this modulation, were studied in GC. We used gene microarrays to screening and luciferase reporter assays were to verify the potential targets of miR-192 and-215. Tissue microarrays analyses were applied to measure the levels of SMG-1 in GC tissues. Western blot assays were used to assess the signaling pathway of SMG-1 regulated by miR-192 and-215 in GC...
December 13, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29239139/btg2-is-a-tumor-suppressor-gene-upregulated-by-p53-and-pten-in-human-bladder-carcinoma-cells
#5
Ke-Hung Tsui, Kun-Chun Chiang, Yu-Hsiang Lin, Kang-Shuo Chang, Tsui-Hsia Feng, Horng-Heng Juang
Although widely deemed as a tumor suppressor gene, the role of B-cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT-qPCR and immunoblotting assays. Expressions of BTG2 and PTEN in bladder carcinoma cells were determined by immunoblotting, RT-qPCR, or reporter assays. The 3 H-thymidine incorporation assay, flow cytometry, and the xenograft animal model were used to determine the cell growth...
December 13, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29238073/stage-dependent-therapeutic-efficacy-in-pi3k-mtor-driven-squamous-cell-carcinoma-of-the-skin
#6
Charbel Darido, Smitha R Georgy, Carleen Cullinane, Darren D Partridge, Rachael Walker, Seema Srivastava, Suraya Roslan, Marina R Carpinelli, Sebastian Dworkin, Richard B Pearson, Stephen M Jane
Cutaneous squamous cell carcinoma (SCC) is a recurrent cancer that is prevalent in predisposed subjects such as immunosuppressed patients and patients being treated for other malignancies. Model systems to trial therapies at different stages of SCC development are lacking, therefore precluding efficient therapeutic interventions. Here, we have disrupted the expression of the tumor suppressor GRHL3 to induce loss of PTEN and activation of the PI3K/mTOR signaling pathway in mice and human skin, promoting aggressive SCC development...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29237774/quantitative-multiplexed-imaging-analysis-reveals-a-strong-association-between-immunogen-specific-b-cell-responses-and-tonsillar-germinal-center-immune-dynamics-in-children-after-influenza-vaccination
#7
Donato Amodio, Nicola Cotugno, Giulia Macchiarulo, Salvatore Rocca, Yiannis Dimopoulos, Maria Rita Castrucci, Rita De Vito, Filippo M Tucci, Adrian B McDermott, Sandeep Narpala, Paolo Rossi, Richard A Koup, Paolo Palma, Constantinos Petrovas
Generation of Ag-specific humoral responses requires the orchestrated development and function of highly specialized immune cells in secondary lymphoid organs. We used a multiparametric approach combining flow cytometry, confocal microscopy, and histocytometry to analyze, for the first time to our knowledge in children, tonsils from seasonal influenza-vaccinated children. We used these novel imaging assays to address the mucosal immune dynamics in tonsils investigating the spatial positioning, frequency, and phenotype of immune cells after vaccination...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29236292/a-novel-report-of-mir-4301-induces-cell-apoptosis-by-negatively-regulating-drd2-expression-in-human-breast-cancer-cells
#8
Naghmeh Gholipour, Anna Ohradanova-Repic, Ghasem Ahangari
BACKGROUND: In several cancers, microRNA (miRNAs) play vital roles in tumour initiation, drug resistance and metastasis. The aim of this study was to examine the expression levels of miR-4301 in human breast cancer and investigate whether its potential roles involved targeting Dopamine receptor D2 (DRD2). METHODS: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was also used to examine the expression levels of miR-4301 in human breast cancer cell lines MDA-MB-231, MCF-7 and SKBR3...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29235674/loss-of-cyld-promotes-cell-invasion-via-alk5-stabilization-in-oral-squamous-cell-carcinoma
#9
Satoru Shinriki, Hirofumi Jono, Manabu Maeshiro, Takuya Nakamura, Jianying Guo, Jian-Dong Li, Mitsuharu Ueda, Ryoji Yoshida, Masanori Shinohara, Hideki Nakayama, Hirotaka Matsui, Yukio Ando
Oral squamous cell carcinoma (OSCC) has a very poor prognosis because of its highly invasive nature, and the 5-year survival rate has not changed appreciably for the past 30 years. Although cylindromatosis (CYLD), a deubiquitinating enzyme, is thought to be a potent tumour suppressor, its biological and clinical significance in OSCC is largely unknown. This study aimed to clarify the roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed significantly reduced CYLD expression in invasive areas in OSCC tissues, whereas CYLD expression was conserved in normal epithelium and carcinoma in situ...
December 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29235573/constitutively-elevated-levels-of-socs1-suppress-innate-responses-in-df-1-immortalised-chicken-fibroblast-cells
#10
E S Giotis, C S Ross, R C Robey, A Nohturfft, S Goodbourn, M A Skinner
The spontaneously immortalised DF-1 cell line is rapidly replacing its progenitor primary chicken embryo fibroblasts (CEFs) for studies on avian viruses such as avian influenza but no comprehensive study has as yet been reported comparing their innate immunity phenotypes. We conducted microarray analyses of DF-1 and CEFs, under both normal and stimulated conditions using chicken interferon-α (chIFN-α) and the attenuated infectious bursal disease virus vaccine strain PBG98. We found that DF-1 have an attenuated innate response compared to CEFs...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235476/breast-cancer-metastasis-suppressor-otud1-deubiquitinates-smad7
#11
Zhengkui Zhang, Yao Fan, Feng Xie, Hang Zhou, Ke Jin, Li Shao, Wenhao Shi, Pengfei Fang, Bing Yang, Hans van Dam, Peter Ten Dijke, Xiaofeng Zheng, Xiaohua Yan, Junling Jia, Min Zheng, Jin Jin, Chen Ding, Sheng Ye, Fangfang Zhou, Long Zhang
Metastasis is the main cause of death in cancer patients. TGF-β is pro-metastatic for malignant cancer cells. Here we report a loss-of-function screen in mice with metastasis as readout and identify OTUD1 as a metastasis-repressing factor. OTUD1-silenced cancer cells show mesenchymal and stem-cell-like characteristics. Further investigation reveals that OTUD1 directly deubiquitinates the TGF-β pathway inhibitor SMAD7 and prevents its degradation. Moreover, OTUD1 cleaves Lysine 33-linked poly-ubiquitin chains of SMAD7 Lysine 220, which exposes the SMAD7 PY motif, enabling SMURF2 binding and subsequent TβRI turnover at the cell surface...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29234933/micrornas-and-metastasis-small-rnas-play-big-roles
#12
Jongchan Kim, Fan Yao, Zhenna Xiao, Yutong Sun, Li Ma
MicroRNAs (miRNAs) are small non-coding RNAs regulating post-transcriptional gene expression. They play important roles in many biological processes under physiological or pathological conditions, including development, metabolism, tumorigenesis, metastasis, and immune response. Over the past 15 years, significant insights have been gained into the roles of miRNAs in cancer. Depending on the cancer type, miRNAs can act as oncogenes, tumor suppressors, or metastasis regulators. In this review, we focus on the role of miRNAs as components of molecular networks regulating metastasis...
December 12, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29234677/metabolic-alterations-of-thyroid-cancer-as-potential-therapeutic-targets
#13
REVIEW
Domenico Ciavardelli, Maria Bellomo, Ada Consalvo, Caterina Crescimanno, Veronica Vella
Thyroid cancer (TC) is the most frequent endocrine tumor with a growing incidence worldwide. Besides the improvement of diagnosis, TC increasing incidence is probably due to environmental factors and lifestyle modifications. The actual diagnostic criteria for TC classification are based on fine needle biopsy (FNAB) and histological examination following thyroidectomy. Since in some cases it is not possible to make a proper diagnosis, classical approach needs to be supported by additional biomarkers. Recently, new emphasis has been given to the altered cellular metabolism of proliferating cancer cells which require high amount of glucose for energy production and macromolecules biosynthesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29234104/conjunction-of-potential-g-quadruplex-and-adjacent-cis-elements-in-the-5-utr-of-hepatocyte-nuclear-factor-4-alpha-strongly-inhibit-protein-expression
#14
Shangdong Guo, Hong Lu
Hepatocyte nuclear factor 4-alpha (HNF4α) is a well established master regulator of liver development and function. We identified the in vitro presence of a stable secondary structure, G-quadruplex (G4) in the 5' UTR of P1-HNF4A, the predominant HNF4α isoform(s) in adult liver. Our data suggest that the cooperation of G4 and the adjacent putative protein-binding sites within the 5' UTR was necessary and sufficient to mediate a strong translational repression. This was supported by analysis of deleted/mutated 5'UTRs and two native regulatory single-nucleotide polymorphisms in the 5'UTR...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234059/p16ink4a-and-p21cip1-waf1-promote-tumour-growth-by-enhancing-myeloid-derived-suppressor-cells-chemotaxis
#15
Atsushi Okuma, Aki Hanyu, Sugiko Watanabe, Eiji Hara
p16Ink4a and p21Cip1/Waf1 act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16Ink4 and p21Cip1/Waf1, namely, tumour promotion through chemotaxis. In monocytic myeloid-derived suppressor cells (Mo-MDSCs), p16Ink4 and p21Cip1/Waf1 are highly expressed and stimulate CX3CR1 chemokine receptor expression by preventing CDK-mediated phosphorylation and inactivation of SMAD3...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233996/pepd-is-a-pivotal-regulator-of-p53-tumor-suppressor
#16
Lu Yang, Yun Li, Arup Bhattacharya, Yuesheng Zhang
p53 tumor suppressor responds to various cellular stresses and regulates cell fate. Here, we show that peptidase D (PEPD) binds and suppresses over half of nuclear and cytoplasmic p53 under normal conditions, independent of its enzymatic activity. Eliminating PEPD causes cell death and tumor regression due to p53 activation. PEPD binds to the proline-rich domain in p53, which inhibits phosphorylation of nuclear p53 and MDM2-mediated mitochondrial translocation of nuclear and cytoplasmic p53. However, the PEPD-p53 complex is critical for p53 response to stress, as stress signals doxorubicin and H2O2 each must free p53 from PEPD in order to achieve robust p53 activation, which is mediated by reactive oxygen species...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233971/implication-of-4e-bp1-protein-dephosphorylation-and-accumulation-in-pancreatic-cancer-cell-death-induced-by-combined-gemcitabine-and-trail
#17
Androulla Elia, Ricky Henry-Grant, Charlotte Adiseshiah, Catherine Marboeuf, Rebecca J Buckley, Michael J Clemens, Satvinder Mudan, Stéphane Pyronnet
Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1...
December 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29233828/e2f1-interacts-with-bcl-xl-and-regulates-its-subcellular-localization-dynamics-to-trigger-cell-death
#18
Céline Vuillier, Steven Lohard, Aurélie Fétiveau, Jennifer Allègre, Cémile Kayaci, Louise E King, Frédérique Braun, Sophie Barillé-Nion, Fabien Gautier, Laurence Dubrez, Andrew P Gilmore, Philippe P Juin, Laurent Maillet
E2F1 is the main pro-apoptotic effector of the pRB-regulated tumor suppressor pathway by promoting the transcription of various pro-apoptotic proteins. We report here that E2F1 partly localizes to mitochondria, where it favors mitochondrial outer membrane permeabilization. E2F1 interacts with BCL-xL independently from its BH3 binding interface and induces a stabilization of BCL-xL at mitochondrial membranes. This prevents efficient control of BCL-xL over its binding partners, in particular over BAK resulting in the induction of cell death...
December 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29233811/dissecting-the-roles-of-the-calcineurin-pathway-in-unisexual-reproduction-stress-responses-and-virulence-in-cryptococcus-deneoformans
#19
Ci Fu, Nicholas Donadio, Maria E Cardenas, Joseph Heitman
The Ca2+/calmodulin-dependent protein phosphatase calcineurin orchestrates sexual reproduction, stress responses, and virulence via branched downstream pathways in the opportunistic human fungal pathogen, Cryptococcus neoformans The calcineurin binding protein Cbp1, the calcineurin temperature suppressor Cts1, the calcineurin responsive zinc finger transcription factor Crz1, and the calcineurin targets Pbp1, Tif3, and Puf4 all function downstream of calcineurin to orchestrate distinct cellular processes. To elucidate how the calcineurin pathway regulatory network governs unisexual reproduction, stress responses, and virulence, we have analyzed the self-filamentous C...
December 12, 2017: Genetics
https://www.readbyqxmd.com/read/29233542/natural-killer-cells-and-anti-tumor-immunity
#20
Sandra E Nicholson, Narelle Keating, Gabrielle T Belz
Immune checkpoint inhibitors harness the power of the immune system to fight cancer. The clinical success achieved with antibodies against the inhibitory T cell receptors PD-1 and CTLA4 has focused attention on the possibility of manipulating other immune cells, in particular those involved in innate immunity. Here we review the role of innate lymphoid cells (ILCs) and their contribution to tumor immunity. As the prototypical ILC, the natural killer (NK) cell has an intrinsic ability to detect and kill cancer cells...
December 9, 2017: Molecular Immunology
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