Abstract：
:Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined. O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities. Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2). PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability. Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT). O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth. These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
journal_name
Oncogenejournal_title
Oncogeneauthors
Singh JP,Qian K,Lee JS,Zhou J,Han X,Zhang B,Ong Q,Ni W,Jiang M,Ruan HB,Li MD,Zhang K,Ding Z,Lee P,Singh K,Wu J,Herzog RI,Kaech S,Wendel HG,Yates JR 3rd,Han W,Sherwin RS,Nie Y,Yang Xdoi
10.1038/s41388-019-0975-3subject
Has Abstractpub_date
2020-01-01 00:00:00pages
560-573issue
3eissn
0950-9232issn
1476-5594pii
10.1038/s41388-019-0975-3journal_volume
39pub_type
杂志文章相关文献
ONCOGENE文献大全abstract：:The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2010.421
更新日期：2011-01-27 00:00:00
abstract：:The forkhead transcription factor FOXM1 has a key role in DNA damage response, and its deregulated overexpression is associated with genotoxic drug resistance in breast cancer. However, little is known about the posttranslational mechanisms by which FOXM1 expression is regulated by genotoxic agents and how they are de...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2015.208
更新日期：2016-03-17 00:00:00
abstract：:Members of the polo subfamily of protein kinases play crucial roles in cell proliferation. To study the function of this family in more detail, we isolated the cDNA of human Fnk (FGF-inducible kinase) which codes for a serine/threonine kinase of 646 aa. Despite the homology to the proliferation-associated polo-like ki...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1203845
更新日期：2000-10-05 00:00:00
abstract：:Zebrafish are making big waves in the field of cancer research. The effect has been widespread and continues to gain speed as more and more cancer researchers ride the wave of zebrafish biology. This has been largely due to the development of transgenic and xenograft models of cancer, which recapitulate many aspects o...
journal_title：Oncogene
pub_type： 杂志文章,评审
doi：10.1038/onc.2008.95
更新日期：2008-07-31 00:00:00
abstract：:BCL11 genes play crucial roles in lymphopoiesis and have been associated with hematopoietic malignancies. Specifically, disruption of the BCL11B (B-cell chronic lymphocytic leukemia/lymphoma 11B) locus is linked to T-cell acute lymphoblastic leukemia, and the loss of heterozygosity in mice results in T-cell lymphoma. ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1208904
更新日期：2005-10-13 00:00:00
abstract：:We recently reported the cloning and overexpression of full-length forms of human fibroblast growth factor (FGF) receptors, bek and flg. These receptors contain three immunoglobulin (Ig)-like domains and an unusual acidic motif in the extracellular region, a single transmembrane segment and a protein tyrosine kinase c...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:With the development of a specific anti-rab2 antiserum, p23rab2, a ras-like GTPase with a -GGGCC C-terminus, has been localized mainly to the particulate (P100) fraction in NIH3T3 cells, although a small amount of this protein also appears in the soluble fraction. The endogenous p23rab2 is isoprenylated in intact cell...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:Somatostatin receptors (sst1-5) are present in different types of tumors, where they inhibit key cellular processes such as proliferation and invasion. Although ssts are densely expressed in breast cancer, especially sst2, their role and therapeutic potential remain uncertain. Recently, we identified a new truncated s...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2011.389
更新日期：2012-04-19 00:00:00
abstract：:The transcription factor nuclear factor kappa B (NF-κB) and the long non-coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) have diverse functional roles in cancer. In this study, we show that upregulation of HOTAIR induced platinum resistance in ovarian cancer, and increased HOTAIR levels were observed in recu...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2016.75
更新日期：2016-10-13 00:00:00
abstract：:Ferritin is the major intracellular iron storage protein that sequesters excess free iron to minimize generation of iron-catalysed reactive oxygen species. We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to pr...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1208901
更新日期：2005-11-17 00:00:00
abstract：:Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2011.260
更新日期：2012-02-02 00:00:00
abstract：:Resistance to chemotherapy remains a critical barrier to effective cancer treatment. Although cisplatin is one of the most commonly used chemotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC), mechanisms of resistance to this drug are not fully understood. Here, we report a novel cisplatin-resi...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-018-0429-3
更新日期：2019-01-01 00:00:00
abstract：:Fas-associated death domain (FADD) is an adaptor protein recruiting complexes of caspase 8 to death ligand receptors to induce extrinsic apoptotic cell death in response to a TNF superfamily member. Although, formation of the complex of FADD and caspase 8 upon death stimuli has been studied in detail, posttranslationa...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-018-0323-z
更新日期：2018-09-01 00:00:00
abstract：:We have found that the differentiation inducer butyric acid causes the synthesis of a cellular protein(s) that mediates a rapid decline in the level of myc RNA in SW837, a cell line derived from a human adenocarcinoma of the rectum. This effect was dose-dependent and was maximal at 1 mM. Among the short chain fatty ac...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Triple-negative breast cancers (TNBCs) are characterized by a poor prognosis and lack of targeted treatments, and thus, new therapeutic strategies are urgently needed. Inhibitors against programmed death-1 (PD-1)/PD-1 ligand (PD-L1) have shown significant efficacy in various solid cancers, but their activity against T...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-019-0700-2
更新日期：2019-05-01 00:00:00
abstract：:The E6 proteins originating from the tumour-associated Human Papillomavirus (HPV) types 16 and 18 have been shown to bind to and target the tumour suppressor protein, p53, for ubiquitin-mediated degradation. However, in cell lines derived from cervical neoplasias, the predominant early region transcripts are spliced a...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201202
更新日期：1997-07-17 00:00:00
abstract：:Rad23 proteins function in both DNA repair and protein stability regulation. As ubiquitinated forms of p53 are stabilized after DNA damage in concert with p53 functional activation, and human Rad23 proteins (hHR23A and B) regulate p53 stability in unstressed cells, the role of hHR23B in post-genotoxin regulation of p5...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1209865
更新日期：2007-02-22 00:00:00
abstract：:NIH sponsored a meeting of medical and veterinary pathologists with mammary gland expertise in Annapolis in March 1999. Rapid development of mouse mammary models has accentuated the need for definitions of the mammary lesions in genetically engineered mice (GEM) and to assess their usefulness as models of human breast...
journal_title：Oncogene
pub_type： 共识发展会议,杂志文章,评审
doi：10.1038/sj.onc.1203277
更新日期：2000-02-21 00:00:00
abstract：:The WARTS gene encodes a kinase that localizes to the mitotic apparatus of a dividing cell. Named WARTS after the growths that develop in the eyes of Drosophila in which the gene is deleted. WARTS is also implicated as a tumor suppressor in mice and humans. In this issue of Oncogene, Iida et al. describe experiments s...
journal_title：Oncogene
pub_type： 评论,杂志文章
doi：10.1038/sj.onc.1207686
更新日期：2004-07-08 00:00:00
abstract：:We examined the biological role of p12(CDK2-AP1) in cisplatin-mediated responses by using murine ES p12(CDK2-AP1) knockout clones generated by a targeted disruption of murine p12(CDK2-AP1). Homozygous knockout clones showed an increased cellular proliferation along with an increase in S and a decrease in G2/M phase po...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1208222
更新日期：2005-01-13 00:00:00
abstract：:We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1202317
更新日期：1999-01-14 00:00:00
abstract：:Mitochondria have been classically characterized as organelles with responsibility for cellular energy production in the form of ATP, but they are also the organelles through which apoptotic signaling occurs. Cell stress stimuli can result in outer membrane permeabilization, after which mitochondria release numerous p...
journal_title：Oncogene
pub_type： 杂志文章,评审
doi：10.1038/onc.2012.348
更新日期：2013-05-30 00:00:00
abstract：:As part of a cloning strategy to identify genes involved in early mouse liver development we have isolated Praja1, a gene with similar sequences to the Drosophila melanogaster gene goliath (gl) which is involved in the fate of mesodermal cells ultimately forming gut musculatures, fat body, and the heart. Praja1 is a 2...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201405
更新日期：1997-11-06 00:00:00
abstract：:The human ryk tyrosine kinase cDNA was originally identified as a PCR-amplified cDNA fragment (JTK5) from K562 leukemia cells and found to represent a ubiquitously expressed gene (Partanen et al., 1990). The open reading frame of human ryk, reported here, encodes a novel type of putative tyrosine kinase of 607 amino a...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:Forkhead box O class transcription factors are homeostasis regulators that control cell death, longevity and therapy-resistance. In neuroblastoma (NB), nuclear FOXO3 correlates with stage M disease and poor prognosis. To analyze whether FOXO3 contributes to drug-resistance in this childhood cancer, we investigated how...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2017.288
更新日期：2017-11-02 00:00:00
abstract：:To study the interplay of steroid hormones and oncogenes in the control of endometrial cell proliferation and differentiation we have generated cell lines derived from rat endometrium by expressing the immortalizing oncogenes adeno E1A or SV40 large T antigen. These lines are positive for mesenchymal markers and conta...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:Estrogen receptor alpha gene (ESR1) mutations occur frequently in ER-positive metastatic breast cancer, and confer clinical resistance to aromatase inhibitors. Expression of the ESR1 Y537S mutation induced an epithelial-mesenchymal transition (EMT) with cells exhibiting enhanced migration and invasion potential in vit...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-020-01563-x
更新日期：2020-12-15 00:00:00
abstract：:The c-Myb, A-Myb and B-Myb transcription factors have nearly identical DNA-binding domains, activate the same reporter gene constructs in animal cells, but have different biological roles. The Myb proteins are often coexpressed in the same cells, raising questions about whether they activate similar or distinct gene e...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1206131
更新日期：2003-01-16 00:00:00
abstract：:Myristoylated Alanine-Rich C Kinase Substrate (MARCKS), a substrate of protein kinase C, is a key regulatory molecule controlling mucus granule secretion by airway epithelial cells as well as directed migration of leukocytes, stem cells and fibroblasts. Phosphorylation of MARKCS may be involved in these responses. How...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2013.336
更新日期：2014-07-10 00:00:00
abstract：:Elevated expression of osteopontin (OPN), a secreted adhesive phosphoglycoprotein, is frequently associated with many transformed cell lines of epithelial and stromal origin. Moreover, several clonal lines of preneoplastic JB6 cells derived from Balb/c mouse epidermal cultures (Colburn et al., 1978, 1979), upon treatm...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
