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Oncogene

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https://www.readbyqxmd.com/read/30232408/klotho-suppresses-colorectal-cancer-through-modulation-of-the-unfolded-protein-response
#1
Tammi Arbel Rubinstein, Shiri Shahmoon, Ehud Zigmond, Tal Etan, Keren Merenbakh-Lamin, Metsada Pasmanik-Chor, Gil Har-Zahav, Iris Barshack, Gilad W Vainer, Nir Skalka, Rina Rosin-Arbesfeld, Chen Varol, Tami Rubinek, Ido Wolf
Klotho is an anti-aging transmembrane protein, which can be shed and function as a hormone. Accumulating data indicate klotho as a tumor suppressor in a wide array of malignancies and indicate the subdomain KL1 as the active region of the protein. We aimed to study the role of klotho as a tumor suppressor in colorectal cancer. Bioinformatics analyses of TCGA datasets indicated reduced klotho mRNA levels in human colorectal cancer, along with negative regulation of klotho expression by hypermethylation of the promoter and 1st exon, and hypomethylation of an area within the gene...
September 19, 2018: Oncogene
https://www.readbyqxmd.com/read/30228349/inositol-polyphosphate-4-phosphatase-type-ii-regulation-of-androgen-receptor-activity
#2
Manqi Zhang, Egla Suarez, Judy L Vasquez, Lubov Nathanson, Leif E Peterson, Kimal Rajapakshe, Paul Basil, Nancy L Weigel, Cristian Coarfa, Irina U Agoulnik
Activation and transcriptional reprogramming of AR in advanced prostate cancer frequently coincides with the loss of two tumor suppressors, INPP4B and PTEN, which are highly expressed in human and mouse prostate epithelium. While regulation of AR signaling by PTEN has been described by multiple groups, it is not known whether the loss of INPP4B affects AR activity. Using prostate cancer cell lines, we showed that INPP4B regulates AR transcriptional activity and the oncogenic signaling pathways Akt and PKC. Analysis of gene expression in prostate cancer patient cohorts showed a positive correlation between INPP4B expression and both AR mRNA levels and AR transcriptional output...
September 18, 2018: Oncogene
https://www.readbyqxmd.com/read/30209363/phosphodiesterase-7b-microrna-200c-relationship-regulates-triple-negative-breast-cancer-cell-growth
#3
Dan-Dan Zhang, Yue Li, Yuan Xu, Jaejik Kim, Shuang Huang
Members of microRNA-200 (miRNA-200) family have a regulatory role in epithelial to mesenchymal transition (EMT) by suppressing Zeb1 and Zeb2 expression. Consistent with its role in suppressing EMT, Hsa-miR-200c-3p (miR-200c), a member of miR-200 family is poorly expressed in mesenchymal-like triple-negative breast cancer (TNBC) cells and ectopic miR-200c expression suppresses cell migration. In this study, we demonstrated that miR-200c potently inhibited TNBC cell growth and tumor development in a mechanism distinct from its ability to downregulate Zeb1 and Zeb2 expression, because silencing them only marginally affected TNBC cell growth...
September 12, 2018: Oncogene
https://www.readbyqxmd.com/read/30209362/oct4b-mediates-hypoxia-induced-cancer-dissemination
#4
Sheng-Chieh Lin, Chi-Hsiu Chung, Chih-Hung Chung, Ming-Han Kuo, Cheng-Han Hsieh, Yu-Fan Chiu, Yi-Shing Shieh, Yu-Ting Chou, Cheng-Wen Wu
Hypoxia, the reduction of oxygen levels in cells or tissues, elicits a set of genes to adjust physiological and pathological demands during normal development and cancer progression. OCT4, a homeobox transcription factor, is essential for self-renewal of embryonic stem cells, but little is known about the role of OCT4 in non-germ-cell tumorigenesis. Here, we report that hypoxia stimulates a short isoform of OCT4, called OCT4B, via a HIF2α-dependent pathway to induce the epithelial-mesenchymal transition (EMT) and facilitate cancer dissemination...
September 12, 2018: Oncogene
https://www.readbyqxmd.com/read/30206359/the-cell-cycle-regulatory-dream-complex-is-disrupted-by-high-expression-of-oncogenic-b-myb
#5
Audra N Iness, Jessica Felthousen, Varsha Ananthapadmanabhan, Fatmata Sesay, Siddharth Saini, Keelan Z Guiley, Seth M Rubin, Mikhail Dozmorov, Larisa Litovchick
Overexpression of the oncogene MYBL2 (B-Myb) is associated with increased cell proliferation and serves as a marker of poor prognosis in cancer. However, the mechanism by which B-Myb alters the cell cycle is not fully understood. In proliferating cells, B-Myb interacts with the MuvB core complex including LIN9, LIN37, LIN52, RBBP4, and LIN54, forming the MMB (Myb-MuvB) complex, and promotes transcription of genes required for mitosis. Alternatively, the MuvB core interacts with Rb-like protein p130 and E2F4-DP1 to form the DREAM complex that mediates global repression of cell cycle genes in G0/G1, including a subset of MMB target genes...
September 11, 2018: Oncogene
https://www.readbyqxmd.com/read/30202098/kiaa1199-promotes-metastasis-of-colorectal-cancer-cells-via-microtubule-destabilization-regulated-by-a-pp2a-stathmin-pathway
#6
Lei Zhao, Dejun Zhang, Qiong Shen, Min Jin, Zhenyu Lin, Hong Ma, Shaoyi Huang, Pengfei Zhou, Gang Wu, Tao Zhang
Tumor metastasis is the main cause of death in advanced colorectal cancer. Our previous research showed that upregulation of KIAA1199 predicted poorer outcomes, and promoted cell motility and tumor metastasis in colorectal cancer, with the mechanisms not being fully elucidated. Here, we demonstrate that silencing of KIAA1199 results in reduced tumor metastasis in the orthotopic transplantation tumor model of colorectal cancer. Importantly, we find that KIAA1199 interacts with protein phosphatase 2A (PP2A) through the C-terminal domain and increases phosphatase activity of PP2A, which is essential for KIAA1199-mediated cell motility...
September 10, 2018: Oncogene
https://www.readbyqxmd.com/read/30202097/loss-of-solute-carrier-family-7-member-2-exacerbates-inflammation-associated-colon-tumorigenesis
#7
Lori A Coburn, Kshipra Singh, Mohammad Asim, Daniel P Barry, Margaret M Allaman, Nicole T Al-Greene, Dana M Hardbower, Dina Polosukhina, Christopher S Williams, Alberto G Delgado, M Blanca Piazuelo, M Kay Washington, Alain P Gobert, Keith T Wilson
Solute carrier family 7 member 2 (SLC7A2, also known as CAT2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in wound repair. We have reported that both SLC7A2 expression and L-Arg availability are decreased in colonic tissues from inflammatory bowel disease patients and that mice lacking Slc7a2 exhibit a more severe disease course when exposed to dextran sulfate sodium (DSS) compared to wild-type (WT) mice. Here, we present evidence that SLC7A2 plays a role in modulating colon tumorigenesis in the azoxymethane (AOM)-DSS model of colitis-associated carcinogenesis (CAC)...
September 10, 2018: Oncogene
https://www.readbyqxmd.com/read/30194451/a-molecular-portrait-of-epithelial-mesenchymal-plasticity-in-prostate-cancer-associated-with-clinical-outcome
#8
Nataly Stylianou, Melanie L Lehman, Chenwei Wang, Atefeh Taherian Fard, Anja Rockstroh, Ladan Fazli, Lidija Jovanovic, Micheal Ward, Martin C Sadowski, Abhishek S Kashyap, Ralph Buttyan, Martin E Gleave, Thomas F Westbrook, Elizabeth D Williams, Jennifer H Gunter, Colleen C Nelson, Brett G Hollier
The propensity of cancer cells to transition between epithelial and mesenchymal phenotypic states via the epithelial-mesenchymal transition (EMT) program can regulate metastatic processes, cancer progression, and treatment resistance. Transcriptional investigations using reversible models of EMT, revealed the mesenchymal-to-epithelial reverting transition (MErT) to be enriched in clinical samples of metastatic castrate resistant prostate cancer (mCRPC). From this enrichment, a metastasis-derived gene signature was identified that predicted more rapid cancer relapse and reduced survival across multiple human carcinoma types...
September 7, 2018: Oncogene
https://www.readbyqxmd.com/read/30194450/vegf-165-b-a-splice-variant-of-vegf-a-promotes-lung-tumor-progression-and-escape-from-anti-angiogenic-therapies-through-a-%C3%AE-1-integrin-vegfr-autocrine-loop
#9
Asma Boudria, Cherine Abou Faycal, Tao Jia, Stephanie Gout, Michelle Keramidas, Chloé Didier, Nicolas Lemaître, Sandra Manet, Jean-Luc Coll, Anne-Claire Toffart, Denis Moro-Sibilot, Corinne Albiges-Rizo, Véronique Josserand, Eva Faurobert, Christian Brambilla, Elisabeth Brambilla, Sylvie Gazzeri, Beatrice Eymin
Vascular endothelial growth factor-A (VEGF-A) is highly subjected to alternative pre-mRNA splicing that generates several splice variants. The VEGFxxx and VEGFxxx b families encode splice variants of VEGF-A that differ only at the level of six amino acids in their C-terminal part. The expression level of VEGFxxx splice variants and their function as pro-angiogenic factors during tumor neo-angiogenesis have been well-described. The role of VEGFxxx b isoforms is less well known, but they have been shown to inhibit VEGFxxx -mediated angiogenesis, while being partial or weak activators of VEGFR receptors in endothelial cells...
September 7, 2018: Oncogene
https://www.readbyqxmd.com/read/30194449/arginine-refolds-stabilizes-and-restores-function-of-mutant-pvhl-proteins-in-animal-model-of-the-vhl-cancer-syndrome
#10
Merav D Shmueli, Limor Levy-Kanfo, Esraa Haj, Alan R Schoenfeld, Ehud Gazit, Daniel Segal
The von Hippel-Lindau (VHL) syndrome is a rare inherited cancer, caused by mutations in the VHL gene, many of which render the VHL protein (pVHL) unstable. pVHL is a tumor-suppressor protein implicated in a variety of cellular processes, most notably in response to changes in oxygen availability, due to its role as part of an E3-ligase complex which targets the hypoxia-inducible factor (HIF) for degradation. Previously we reported, using in silico and in vitro analyses, that common oncogenic VHL mutations render pVHL less stable than the wild-type protein, distort its core domain and as a result reduce the ability of the protein to bind its target HIF-1α...
September 7, 2018: Oncogene
https://www.readbyqxmd.com/read/30190546/premature-activation-of-cdk1-leads-to-mitotic-events-in-s-phase-and-embryonic-lethality
#11
Radoslaw Szmyd, Joanna Niska-Blakie, M Kasim Diril, Patrícia Renck Nunes, Konstantinos Tzelepis, Aurélie Lacroix, Noémi van Hul, Lih-Wen Deng, Joao Matos, Oliver Dreesen, Xavier Bisteau, Philipp Kaldis
Cell cycle regulation, especially faithful DNA replication and mitosis, are crucial to maintain genome stability. Cyclin-dependent kinase (CDK)/cyclin complexes drive most processes in cellular proliferation. In response to DNA damage, cell cycle surveillance mechanisms enable normal cells to arrest and undergo repair processes. Perturbations in genomic stability can lead to tumor development and suggest that cell cycle regulators could be effective targets in anticancer therapy. However, many clinical trials ended in failure due to off-target effects of the inhibitors used...
September 6, 2018: Oncogene
https://www.readbyqxmd.com/read/30190545/role-of-sumoylation-in-differential-er%C3%AE-transcriptional-repression-by-tamoxifen-and-fulvestrant-in-breast-cancer-cells
#12
Tatiana Traboulsi, Mohamed El Ezzy, Vanessa Dumeaux, Eric Audemard, Sylvie Mader
Antiestrogens (AEs) are widely used for treatment of estrogen receptor alpha (ERα)-positive breast cancer, but display variable degrees of partial agonism in estrogen target tissues and breast cancer (BC) cells. The fact that BC cells resistant to selective ER modulators (SERMs) like tamoxifen (Tam) can still be sensitive to pure AEs, also called selective ER downregulators, suggests different mechanisms of action, some of which may contribute to the more complete suppression of estrogen target genes by pure AEs...
September 6, 2018: Oncogene
https://www.readbyqxmd.com/read/30185813/jmjd6-regulates-histone-h2a-x-phosphorylation-and-promotes-autophagy-in-triple-negative-breast-cancer-cells-via-a-novel-tyrosine-kinase-activity
#13
Yan Liu, Yue-Hong Long, Shu-Qing Wang, Yuan-Yue Zhang, Yu-Feng Li, Jiang-Sheng Mi, Cheng-Hua Yu, De-Yan Li, Jing-Hua Zhang, Xiao-Jun Zhang
Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph ). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes...
September 5, 2018: Oncogene
https://www.readbyqxmd.com/read/30181549/myeov-functions-as-an-amplified-competing-endogenous-rna-in-promoting-metastasis-by-activating-tgf-%C3%AE-pathway-in-nsclc
#14
Lishan Fang, Shanshan Wu, Xun Zhu, Junchao Cai, Jueheng Wu, Zhenjian He, Lei Liu, Musheng Zeng, Erwei Song, Jun Li, Mengfeng Li, Hongyu Guan
Non-small cell lung cancer (NSCLC) remains a major cause of death worldwide. As metastatic disease is primarily responsible for the poor clinical outcome of NSCLC, it is important to understand the process, and its underlying molecular mechanism as well, via which NSCLC cells disseminate. In this study, we identified a new competing endogenous RNA (ceRNA), namely, the MYEOV transcript, and found that it is upregulated in NSCLC and associated with a poor prognosis of the disease. We further uncovered that the MYEOV ceRNA plays a critical role in the invasion and metastasis of NSCLC cells...
September 4, 2018: Oncogene
https://www.readbyqxmd.com/read/30181548/dedifferentiation-process-driven-by-tgf-beta-signaling-enhances-stem-cell-properties-in-human-colorectal-cancer
#15
Michitaka Nakano, Yoshikane Kikushige, Kohta Miyawaki, Yuya Kunisaki, Shinichi Mizuno, Katsuto Takenaka, Shingo Tamura, Yuta Okumura, Mamoru Ito, Hiroshi Ariyama, Hitoshi Kusaba, Masafumi Nakamura, Takahiro Maeda, Eishi Baba, Koichi Akashi
Cancer stem cells (CSCs) possess the capacity for self-renewal and the potential to differentiate into non-CSCs. The recent discoveries of dynamic equilibrium between CSCs and non-CSCs revealed the significance of acquiring CSC-like properties in non-CSCs as an important process in progression of cancer. The mechanism underlying acquisition of CSC-like properties has mainly been investigated in the context of epithelial-mesenchymal transition. Here, we demonstrate the dedifferentiation process may be an alternative mechanism in acquisition of CSC-like properties in human colorectal cancer cells...
September 4, 2018: Oncogene
https://www.readbyqxmd.com/read/30181547/gabpa-inhibits-invasion-metastasis-in-papillary-thyroid-carcinoma-by-regulating-dicer1-expression
#16
Xiaotian Yuan, Ninni Mu, Na Wang, Klas Strååt, Anastasios Sofiadis, Yanxia Guo, Adam Stenman, Kailin Li, Guanghui Cheng, Lu Zhang, Feng Kong, Lars Ekblad, Johan Wennerberg, Inga-Lena Nilsson, C Christofer Juhlin, Catharina Larsson, Dawei Xu
The ETS family transcription factor GABPA is suggested as an oncogenic element, which is further supported by the recent reporting of it as the sole ETS member to activate the mutant TERT promoter in thyroid carcinomas (TC). However, it remains unclear how GABPA contributes to TC pathogenesis. The present study is designed to address this issue. TERT expression was significantly diminished in TERT promoter-mutated TC cells upon GABPA inhibition. Surprisingly, GABPA depletion led to robustly increased cellular invasion independently of TERT promoter mutations and TERT expression...
September 4, 2018: Oncogene
https://www.readbyqxmd.com/read/30177842/hmgb1-correlates-with-angiogenesis-and-poor-prognosis-of-perihilar-cholangiocarcinoma-via-elevating-vegfr2-of-vessel-endothelium
#17
Yun-Fei Xu, Zeng-Li Liu, Chang Pan, Xiao-Qing Yang, Shang-Lei Ning, Hong-Da Liu, Sen Guo, Jin-Ming Yu, Zong-Li Zhang
Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR...
September 3, 2018: Oncogene
https://www.readbyqxmd.com/read/30177841/gjb4-serves-as-a-novel-biomarker-for-lung-cancer-and-promotes-metastasis-and-chemoresistance-via-src-activation
#18
Yi-Pei Lin, Jun-I Wu, Chien-Wei Tseng, Huei-Jane Chen, Lu-Hai Wang
Most lung cancer patients are diagnosed late with metastasis, which is the major cause of cancer-related death and recurrent tumors that often exhibit chemoresistance. In the present study, we initially identified gap junction beta-4 protein (Gjb4) to be overexpressed in highly metastatic cancer cells selected by their enhanced binding to serum components. Overexpression or knockdown of Gjb4 increased or decreased lung metastasis of syngeneic mice, respectively. We found that Gjb4 expression was higher in lung tumors than normal tissues (p = 0...
September 3, 2018: Oncogene
https://www.readbyqxmd.com/read/30177840/tpx2-aurora-kinase-a-signaling-as-a-potential-therapeutic-target-in-genomically-unstable-cancer-cells
#19
Stephanie E van Gijn, Elles Wierenga, Nathalie van den Tempel, Yannick P Kok, Anne Margriet Heijink, Diana C J Spierings, Floris Foijer, Marcel A T M van Vugt, Rudolf S N Fehrmann
Genomic instability is a hallmark feature of cancer cells, and can be caused by defective DNA repair, for instance due to inactivation of BRCA2. Paradoxically, loss of Brca2 in mice results in embryonic lethality, whereas cancer cells can tolerate BRCA2 loss. This holds true for multiple DNA repair genes, and suggests that cancer cells are molecularly "rewired" to cope with defective DNA repair and the resulting high levels of genomic instability. In this study, we aim to identify genes that genomically unstable cancer cells rely on for their survival...
September 3, 2018: Oncogene
https://www.readbyqxmd.com/read/30177839/transcriptional-repression-of-ikk%C3%AE-by-p53-in-arsenite-induced-gadd45%C3%AE-accumulation-and-apoptosis
#20
Yongliang Hu, Rui Jin, Ming Gao, Huan Xu, Shuxian Zou, Xiaoguang Li, Chen Xing, Qiyu Wang, Hongli Wang, Jiannan Feng, Meiru Hu, Lun Song
Our previous studies revealed that GADD45α is a liable protein, which undergoes MDM2-dependent constitutive ubiquitination and degradation in resting HepG2 hepatoma cells. Arsenite exposure induces ribosomal stress responses mediated by the ribosomal protein S7, which can block MDM2 activity and result in GADD45α accumulation and cell apoptosis. In the present study, we found that one of the catalytic subunits of IκB kinase (IKK), IKKβ, exerted a novel IKKα- and NF-κB-independent function in stabilizing MDM2 and therefore contributed to ubiquitination-dependent degradation of GADD45α in resting HepG2 cells...
September 3, 2018: Oncogene
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