Abstract:
:The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradiation showed decreased oxygen consumption and increased glycolysis with compromised mitochondria, corresponding with their enhanced sensitivity to drugs that target glycolysis. In contrast, radioresistant cancer cells with wild-type p53 preserved their primary metabolic profile with intact mitophagic processes and maintained their mitochondrial integrity. Moreover, we identified a previously unappreciated link between p53 and mitophagy, which limited the glycolytic shift through the BNIP3-dependent clearance of abnormal mitochondria. Thus, drugs targeting glycolysis could be used as an alternative strategy for overcoming radioresistant cancers, and the p53 status could be used as a biomarker for selecting participants for clinical trials.
journal_name
Oncogenejournal_title
Oncogeneauthors
Chang HW,Kim MR,Lee HJ,Lee HM,Kim GC,Lee YS,Nam HY,Lee M,Jang HJ,Lee KE,Lee JC,Byun Y,Kim SW,Kim SYdoi
10.1038/s41388-019-0697-6subject
Has Abstractpub_date
2019-05-01 00:00:00pages
3729-3742issue
19eissn
0950-9232issn
1476-5594pii
10.1038/s41388-019-0697-6journal_volume
38pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Mice bred to carry germline Rb and p53 null alleles are associated with a tumor spectrum that overlaps with the inherited multiple endocrine neoplasia-1 (MEN1) and MEN2 syndromes in humans, including medullary thyroid cancer (MTC). To study the genetic basis for these tumors, we microdissected MTC specimens or obtaine...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202381
更新日期:1998-09-24 00:00:00
abstract::The BRCA1-associated RING domain protein BARD1 acts with BRCA1 in double-strand break repair and ubiquitination. BARD1 plays a role as mediator of apoptosis by binding to and stabilizing p53, and BARD1-repressed cells are resistant to apoptosis. We therefore investigated the mechanism by which BARD1 induces p53 stabil...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208491
更新日期:2005-05-26 00:00:00
abstract::Histone deacetylases (HDACs) negatively regulate gene expression by removing acetyl groups from lysine residues present in histones and other proteins. Histone deacetylase 3 is unique among the Class I family of HDACs, as it is able to shuttle between the nucleus and the cytoplasm, whereas the other family members rem...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209473
更新日期:2006-07-27 00:00:00
abstract::We have established conditions for the immortalization of human fibroblasts by the large T antigen of the rodent virus polyoma. This allows the mechanism of immortalization to be studied, without interference by transformation events, in cells with relatively stable chromosomes. Large T antigen could immortalize human...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and remains incurable with conventional chemotherapy treatment approaches. CLL as a disease entity is defined by a relatively parsimonious set of diagnostic criteria and therefore likely constitutes an umbrella term for multiple relate...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2012.411
更新日期:2013-06-06 00:00:00
abstract::Mdm2, a regulator of the p53 tumor suppressor, is frequently overexpressed in lymphomas, including lymphomas that have inactivated p53. However, the biological consequences of Mdm2 overexpression in lymphocytes are not fully resolved. Here, we report that increased expression of Mdm2 in B cells augmented proliferation...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210788
更新日期:2008-03-06 00:00:00
abstract::Loss of RASSF1A leads to several mitotic abnormalities, including cytokinesis failure and tetraploidization. Uncontrolled proliferation of tetraploid cells is known to trigger genomic instability and tumor development and is normally prevented through activation of a p53-dependent tetraploidy checkpoint. RASSF1A is th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.440
更新日期:2011-02-10 00:00:00
abstract::We have previously determined that the amplified DNA present in the HL60 promyelocytic leukaemia cell line contained 70 kb of continuous DNA sequences around the c-myc gene. In the work presented here we have further defined the HL60 amplicon and find it to be of the order of 160 kb and to contain a large region of DN...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-10-03 00:00:00
abstract::We have previously reported that carboxyl terminal truncations of the normal human fyn gene, a member of the src subfamily, can transform immortal mouse fibroblasts to full malignancy. In search of evidence which suggests the possible activation of the human fyn gene, we have screened DNAs and RNAs from a number of hu...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Deletions involving chromosome 9 occur in more than 50% of human bladder cancers of all grades and stages. Most involve loss of the whole chromosome or of an entire chromosome arm but some small deletions are found which can be used to define critical regions which may contain tumour suppressor genes. We have localize...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202854
更新日期:1999-04-22 00:00:00
abstract::Functional alterations or loss of tumor-suppressor genes are an important feature of neoplastic progression in humans. The employment of suitable animal model systems would greatly facilitate the detection and manipulation of such genes. We describe here an experimental approach to this problem based on the analysis o...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::Chromosomal translocation t(X;14)(q28;q11) has been observed in patients with pro-lymphocytic T-cell leukaemia (T-PLL). In two cases of T-PLL, one of which was associated with Ataxia telangiectasia (AT), the chromosomal break occurred in two different introns of a gene c6.1A, located at the Xq28 locus. Fusion transcri...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Bcl-2 and Bcl-XL serve as critical inhibitors of apoptosis triggered by a broad range of stimuli, mainly acting on the mitochondria. We identified two members of the reticulon (RTN) family as Bcl-XL binding proteins, i.e., NSP-C (RTN1-C) and a new family member, RTN-XS, both of which did not belong to the Bcl-2 family...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203948
更新日期:2000-11-23 00:00:00
abstract::The candidate proto-oncogene BCL3 was isolated through its involvement in the t(14;19) found in chronic lymphocytic leukemia and other B-cell neoplasms. As a member of the I kappaB family, BCL3 plays a role in the immune response by interactions with the NF-kappaB family of transcription factors. In order to study the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201771
更新日期:1998-05-07 00:00:00
abstract::Loss of p53 function is associated with the acquisition of cisplatin resistance in the human ovarian adenocarcinoma A2780 cell line. Selection for cisplatin resistance of A2780 cells was used to isolate genetic suppressor elements (GSEs) from a retroviral library expressing random fragments of human or murine TP53 cDN...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200813
更新日期:1997-01-16 00:00:00
abstract::Tumor cells, stromal cell compartment and the extracellular matrix (ECM) together generate a multifaceted tumor microenvironment. Matrix metalloproteinases and their tissue inhibitors (TIMPs) provide a means for tumor-stromal interaction during tumorigenesis. Among TIMPs, TIMP-3 is uniquely localized to the ECM and is...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209104
更新日期:2006-01-26 00:00:00
abstract::Identifying novel and known genes that are differentially expressed in breast cancer has important implications in understanding the biology of breast tumorigenesis and developing new diagnostic and therapeutic agents. In this study we have combined two powerful technologies, PCR-based cDNA subtraction and cDNA microa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205278
更新日期:2002-03-28 00:00:00
abstract::FLT3 tyrosine kinase domain (TKD) mutations are detected in approximately 7% of acute myeloid leukemia patients, and suggested to correlate with poor prognosis and confer resistance to FLT3 inhibitors. To explore activation mechanism of FLT3 TKD mutation, we analysed critical tyrosine residues for the constitutive act...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208957
更新日期:2005-12-08 00:00:00
abstract::In this study we have investigated DNA-protein interactions at an AP1-like motif of the neuropeptide tyrosine (NPY) promoter during in vitro differentiation of human neuroblastoma cells SH-SY5Y to mature nonproliferative sympathetic neuron-like cells. These neuroblast-like cells originate from the parental cell line S...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas that frequently arise in patients with neurofibromatosis type 1 (NF1). Most of these tumors are unresectable at diagnosis and minimally responsive to conventional treatment, lending urgency to the identification of new pathway dependencies and ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0965-5
更新日期:2019-09-01 00:00:00
abstract::The etiology of cancers appears to be complex and multifactorial. Peyton Rous and others demonstrated the process of co-carcinogenesis by exposing rabbits to a virus and tars. Epidemiologists have proposed virus-chemical interactions to cause several cancers. For example, one might propose that the etiology of cervica...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1207822
更新日期:2004-08-23 00:00:00
abstract::Rad54 and Mus81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway; however, their functional interactions in vivo are poorly defined. Here, we show that combinatorial loss of Rad54 and Mus81 results in hypersensitivity to DNA-damaging agents, defects on both t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.16
更新日期:2016-09-15 00:00:00
abstract::Normal human melanocytes are interspersed singly among keratinocytes along the basement membrane of the epidermis, whereas melanoma cells readily adhere to each other during invasion of the dermis or distant organs. The tumorigenic and metastatic phenotype of melanoma cells often correlates with increased expression o...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204616
更新日期:2001-08-02 00:00:00
abstract::Cancer therapy drugs, such as diamminedichloroplatinum (cisplatin), mitomycin C, etoposide and a number of other compounds, as well as energy-rich radiation, are known to act on cellular DNA. These agents are shown to induce nuclear accumulation of the so-called tumor-suppressor protein p53 in fibroblastoid cells, as ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Signet-ring cell carcinoma is classified in poorly differentiated adenocarcinoma with an aggressive nature and a poor prognosis. We have shown that the activation of PI 3-kinase in highly differentiated adenocarcinomas induces loss of cell-cell contact and formation of vacuoles, giving phenotypes similar to those of s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206796
更新日期:2003-08-28 00:00:00
abstract::We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201460
更新日期:1997-09-04 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) all signal through the transmembrane receptor tyrosine kinase RET. The signalling complex consists of GFLs, GPI-anchored ligand binding GDNF family receptor alphas (GFRalphas) and RET. Signalling via RET is required for the development of the ner...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210161
更新日期:2007-05-31 00:00:00
abstract::The human tumor suppressor gene ataxia telangiectasia mutated (ATM) encodes a 3056 amino-acid protein kinase that regulates cell cycle checkpoints. ATM is defective in the neurodegenerative and cancer predisposition syndrome ataxia-telangiectasia. ATM protein kinase is activated by DNA damage and responds by phosphory...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206649
更新日期:2003-06-19 00:00:00
abstract::Ataxia Telangiectasia Mutated (ATM) kinase, a central regulator of the DNA damage response, regulates the activity of several E3-ubiquitin ligases, and the ubiquitination-proteasome system is a consistent target of ATM. ITCH is an E3-ubiquitin ligase that modulates the ubiquitination of several targets, therefore part...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.52
更新日期:2014-02-27 00:00:00
abstract::In Xiphophorus the causative, primary cellular oncogene for melanoma formation has been assigned by classical genetics to a sex-chromosomal locus, designated Tu. Activation of Tu was proposed to be the result of the elimination of Tu-specific regulatory genes which normally suppress the transforming function in the no...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00