Abstract:
:Enhanced glucose and lipid metabolism is one of the most common properties of malignant cells. ATP citrate lyase (ACLY) is a key enzyme of de novo fatty acid synthesis responsible for generating cytosolic acetyl-CoA and oxaloacetate. To evaluate its role in lung cancer progression, we here analyzed ACLY expression in a subset of human lung adenocarcinoma cell lines and showed a relationship with the phosphatidyl-inositol-3 kinase-Akt pathway. The introduction of constitutively active Akt into cells enhanced the phosphorylation of ACLY, whereas dominant-negative Akt caused attenuation. In human lung adenocarcinoma samples, ACLY activity was found to be significantly higher than in normal lung tissue. Immunohistochemical analysis further showed phosphorylated ACLY overexpression in 162 tumors, well-correlating with stage, differentiation grade, and a poorer prognosis. Finally, to show the therapeutic potential and mechanism of ACLY inhibition for lung cancer treatment, we assessed the effect of RNA interference targeting ACLY on lipogenesis and cell proliferation in A549 cells. ACLY inhibition resulted in growth arrest in vitro and in vivo. Interestingly, increased intracellular lipids were found in ACLY knockdown cells, whereas de novo lipogenesis was inhibited. Supplementation of insulin could rescue the proliferative arrest elicited by ACLY inhibition; however, in contrast, fatty acid palmitate induced cell death. Taken together, these findings suggest that ACLY is involved in lung cancer pathogenesis associated with metabolic abnormality and might offer a novel therapeutic target.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Migita T,Narita T,Nomura K,Miyagi E,Inazuka F,Matsuura M,Ushijima M,Mashima T,Seimiya H,Satoh Y,Okumura S,Nakagawa K,Ishikawa Ydoi
10.1158/0008-5472.CAN-08-1235subject
Has Abstractpub_date
2008-10-15 00:00:00pages
8547-54issue
20eissn
0008-5472issn
1538-7445pii
68/20/8547journal_volume
68pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The ability of tumor cells to express elevated levels of proteinases capable of degrading tissue matrix and basement membrane components in vitro has been correlated to their invasive and metastatic potential. Many in vitro invasion assays have been performed either in the presence of serum or with tumor cells that ha...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-15 00:00:00
abstract::Curcumin, a plant polyphenol, is a widely studied chemopreventive agent with demonstrated antitumor activities in preclinical studies and low toxicity profiles in multiple clinical trials against human malignancies. We previously showed that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3025
更新日期:2010-03-01 00:00:00
abstract::Natural killer (NK) immune cells mediate antibody-dependent cellular cytotoxicity (ADCC) by aggregating FcγRIIIA/CD16, contributing significantly to the therapeutic effect of CD20 monoclonal antibodies (mAb). In this study, we show that CD16 ligation on primary human NK cells by the anti-CD20 mAb rituximab or ofatumum...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-0781
更新日期:2015-10-01 00:00:00
abstract::The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma ti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1890
更新日期:2005-03-15 00:00:00
abstract::cis- and trans-diamminedichloroplatinum(II) (PDD) produced a DNA cross-linking effect in mouse leukemia L1210 cells, which was demonstrable after subtoxic treatments with the DNA alkaline elution technique. Cross-linking effects developed following treatments with concentrations as low as 1 micron for cis-PDD and 5 mi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-06-01 00:00:00
abstract::Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis, and metastasis. Macrophages are also the key effector cell for mAb therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM), which favors expression of in...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-2784
更新日期:2017-07-01 00:00:00
abstract::Aniline of unknown purity has been reported to induce spleen hemangiosarcoma in rats. Aniline has been found to be negative in terms of mutagenicity in both bacteria and yeasts. We have found that both commercial (already rather pure) and repurified aniline are clearly positive to a similar extent in inducing DNA dama...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-06-01 00:00:00
abstract::By subjecting radiosensitive human neuroblastoma IMR 32 cells to a regime of fractionated X-irradiation, a radioresistant variant, XRIMR 32, was obtained. Radiation resistance of XRIMR 32 cells was demonstrated by clonogenic and spheroid regrowth delay assays. The XRIMR 32 cultures were phenotypically unstable, with t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Copy number alterations are crucial for the development of colorectal cancer. Our whole-genome analysis identified tocopherol alpha transfer protein-like (TTPAL) as preferentially amplified in colorectal cancer. Here we demonstrate that frequent copy number gain of TTPAL leads to gene overexpression in colorectal canc...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-2986
更新日期:2019-07-01 00:00:00
abstract::To better understand immune responses to brain tumors and to develop possible approaches for immunotherapy, we have investigated the leukocyte populations infiltrating the rat 9L gliosarcoma. By immunocytochem-ical analyses of the cells infiltrating the tumor, we observed a substantial number of cells expressing natur...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::The deleted in colorectal cancer (DCC) gene, a candidate tumor suppressor gene on chromosome 18q21, encodes a neural cell adhesion molecule family protein that is most highly expressed in the nervous system. To address the hypothesis that DCC may play a role in glioma development and/or progression, we examined DCC ex...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::2-Methoxyestradiol (2ME(2)), a physiologic metabolite of 17beta-estradiol (estrogen), has emerged as a promising cancer therapy because of its potent growth-inhibitory and proapoptotic effects on both endothelial and tumor cells. 2ME(2) also suppresses osteoclast differentiation and induces apoptosis of mature osteocl...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1362
更新日期:2007-11-01 00:00:00
abstract::This study investigated the effect of recombinant human tumor necrosis factor (rhTNF) on hydroxyl radical production by established cell lines in vitro, and its implication in the killing of tumor cells by rhTNF. During incubation of TNF sensitive mouse tumorigenic fibroblast L-M cells (2 X 10(7) cells) in the presenc...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Successful treatment of many patients with osteosarcoma requires more effective chemotherapy. Since new agents are needed, we have developed an immunotoxin using TP-3, an IgG2b mAb which recognizes human and canine osteosarcomas and budding capillaries of tumors. The plant hemitoxin, pokeweed antiviral protein (PAP), ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-03-15 00:00:00
abstract::Protein kinases of the Raf family act as signal-transducing elements downstream of activated cell surface receptors and are involved in the regulation of proliferation, differentiation, and cell survival. Whereas the role of c-Raf-1 as a mitogen-activated protein/extracellular signal-regulated kinase activator within ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-07-15 00:00:00
abstract::Although altered expression of platelet-derived growth factor (PDGF)-A is a hallmark of many cancers, the importance of pro-PDGF-A conversion to PDGF-A in tumorigenesis and the cognate protease(s) is unknown. Pro-PDGF-A processing occurs at pairs of basic residues, likely involving the proprotein convertases (PCs). In...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract::Reported estimates of ras mutation prevalence in lung adenocarcinoma of 15-24% may be underestimates because of the insensitivity of the assays used. We have devised a rapid, non-radioactive assay for ras mutations, which detects 1 mutant allele/10(3) normal alleles and have used it to study DNA isolated from 53 lung ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Genetic instability has been recognized as a hallmark of human cancers. Retinoblastoma (Rb) tumor suppressor protein has an essential role in modulating cell cycle progression. However, there is no direct evidence supporting its role in maintaining genetic stability. Here, we developed a sensitive method to examine th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
abstract::Fischer X Copenhagen rats bearing Dunning R3327-AT tumors were treated with hematoporphyrin derivative and red light (630 nm from an argon-driven dye laser) alone or in combination with the hypoxic cell radiosensitizer, misonidazole (MISO). In vitro studies had suggested that hypoxia might significantly decrease the c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::To examine genetic instability during carcinogenesis, we screened 171 carcinomas of the breast, liver, proximal colon, stomach, pancreas, uterine cervix, and ovary for replication error at four microsatellite marker loci on chromosome 2, 3, and 17. A significantly high incidence of genetic instability was observed in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::To identify mechanisms of camptothecin (CPT) resistance/toxicity, sublines from a human KB cell line were made resistant to CPT by continuous selection in increasing concentrations of CPT. Two CPT-resistant lines, 100 and 300, were 32- and 54-fold resistant to the growth-inhibitory properties of CPT compared to the KB...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-01-15 00:00:00
abstract::Molecular markers of pancreatic neoplasia could aid in the evaluation of visible pancreatic lesions and indicate neoplasia invisible to imaging. We evaluated methylation-specific PCR (MSP) assays that detect aberrantly methylated DNA for their use as markers of pancreatic neoplasia. Methylation analysis was done on pa...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:10.1158/0008-5472.CAN-05-2664
更新日期:2006-01-15 00:00:00
abstract::Mouse leukemia (P388) cells were incubated in cell culture medium containing nitrogen mustard [2-chloro-N-(2-chloroethyl)-N-methylethanamine] for 4 h. The nucleophosmin immunoband with a molecular weight of 37,000 (p37; other molecular weights are similarly designated) was observed in both control and nitrogen mustard...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-06-15 00:00:00
abstract::To elucidate the role of cyclin E in cell growth and tumorigenesis in mammary epithelial cells, we have used retrovirus-mediated transduction to generate derivatives of the nontransformed HC11 mouse mammary epithelial cell line that stably express a human cyclin E cDNA (HU4). These derivatives expressed two distinct f...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-03-15 00:00:00
abstract::Putative preneoplastic hepatocytes were isolated from male Fischer 344 rats treated with a single dose of diethylnitrosamine, 2-acetylaminofluorene feeding, and partial hepatectomy (Solt-Farber model). The isolation procedure involved, after collagenase dispersion of the liver, separation of the hepatocytes into small...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
abstract::Testicular germ cell tumors (TGCT) are the most common solid tumors of 15- to 35-year-old men. TGCT patients are frequently cured with cytotoxic cisplatin-based therapy. However, TGCT patients refractory to cisplatin-based chemotherapy have a poor prognosis, as do those having a late relapse. Pluripotent embryonal car...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1490
更新日期:2009-12-15 00:00:00
abstract::Alterations in cellular biochemistry which are associated with the development of resistance to cytotoxic peptides, such as tumor necrosis factor (TNF), may also be responsible for changes in the response of cells to cytotoxic agents. Culturing ME-180 cervical carcinoma cells in the presence of escalating concentratio...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::The cellular effects of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and N1,N8-bis(ethyl)spermidine (BES), an apparent regulator of the enzyme were compared in cultured L1210 cells. Unlike DFMO, BES has no direct inhibitory effect on ODC activity. Rather the polyamine analogue i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::CC-1065, a novel antibiotic produced by Streptomyces zelensis, was active against several experimental tumors in vivo and a broad spectrum of human tumor cells in vitro. This report describes its biological and biochemical effects of L1210 leukemia cells. CC-1065 is one of the most cytotoxic agents known. The concentr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells)...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00