当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth.

Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth.

Abstract：

:The relevance of cysteine metabolism in cancer has gained considerable interest in recent years, largely focusing on its role in generating the antioxidant glutathione. Through metabolomic profiling using a combination of high-throughput liquid and gas chromatography-based mass spectrometry on a total of 69 patient-derived glioma specimens, this report documents the discovery of a parallel pathway involving cysteine catabolism that results in the accumulation of cysteine sulfinic acid (CSA) in glioblastoma. These studies identified CSA to rank as one of the top metabolites differentiating glioblastoma from low-grade glioma. There was strong intratumoral concordance of CSA levels with expression of its biosynthetic enzyme cysteine dioxygenase 1 (CDO1). Studies designed to determine the biologic consequence of this metabolic pathway identified its capacity to inhibit oxidative phosphorylation in glioblastoma cells, which was determined by decreased cellular respiration, decreased ATP production, and increased mitochondrial membrane potential following pathway activation. CSA-induced attenuation of oxidative phosphorylation was attributed to inhibition of the regulatory enzyme pyruvate dehydrogenase. Studies performed in vivo abrogating the CDO1/CSA axis using a lentiviral-mediated short hairpin RNA approach resulted in significant tumor growth inhibition in a glioblastoma mouse model, supporting the potential for this metabolic pathway to serve as a therapeutic target. Collectively, we identified a novel, targetable metabolic pathway involving cysteine catabolism contributing to the growth of aggressive high-grade gliomas. These findings serve as a framework for future investigations designed to more comprehensively determine the clinical application of this metabolic pathway and its contributory role in tumorigenesis.

journal_name

Cancer Res

journal_title

Cancer research

authors

Prabhu A,Sarcar B,Kahali S,Yuan Z,Johnson JJ,Adam KP,Kensicki E,Chinnaiyan P

doi

10.1158/0008-5472.CAN-13-1423

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

787-96

issue

3

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-13-1423

journal_volume

74

pub_type

杂志文章

相关文献

CANCER RESEARCH文献大全
  • High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation.

    abstract：:A novel method for high-efficiency and region- controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Nishi T,Yoshizato K,Yamashiro S,Takeshima H,Sato K,Hamada K,Kitamura I,Yoshimura T,Saya H,Kuratsu J,Ushio Y

    更新日期：1996-03-01 00:00:00

  • Cancer suppression at old age.

    abstract：:Increased age is regularly linked with heightened cancer risk, but recent research suggests a flattening around age 80. We report that, independent of cancer site or time period, most incidence rates decrease in the more elderly and drop to or toward zero near the ceiling of human life span. For all major organ sites,...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-07-1670

    authors： Harding C,Pompei F,Lee EE,Wilson R

    更新日期：2008-06-01 00:00:00

  • Specific p53 gene mutations in urinary bladder epithelium after the Chernobyl accident.

    abstract：:After the Chernobyl accident, the incidence of urinary bladder cancers in the Ukraine population increased gradually from 26.2 to 36.1 per 100,000 between 1986 and 1996. Urinary bladder epithelium biopsied from 45 male patients with benign prostatic hyperplasia living in radiocontaminated areas of Ukraine demonstrated...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Yamamoto S,Romanenko A,Wei M,Masuda C,Zaparin W,Vinnichenko W,Vozianov A,Lee CC,Morimura K,Wanibuchi H,Tada M,Fukushima S

    更新日期：1999-08-01 00:00:00

  • Partial characterization of insulin-like growth factor I in primary human lung cancers using immunohistochemical and receptor autoradiographic techniques.

    abstract：:We investigated primary human lung cancers resected surgically or obtained at autopsy. Included were squamous cell carcinoma (SQC) (five cases), adenocarcinoma (ADC) (six cases), large cell carcinoma (LCC) (four cases), and small cell carcinoma (SCC) (two cases). The objective of the study was to search for the presen...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Shigematsu K,Kataoka Y,Kamio T,Kurihara M,Niwa M,Tsuchiyama H

    更新日期：1990-04-15 00:00:00

  • Long-term adjuvant therapy with tamoxifen: effects on sex hormone binding globulin and antithrombin III.

    abstract：:Plasma levels of luteinizing hormone, sex hormone binding globulin, and antithrombin III were measured in pre- and postmenopausal breast cancer patients receiving adjuvant combination chemotherapy or combination chemotherapy and long-term tamoxifen therapy. The aim was to determine the estrogen-like effects of tamoxif...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Jordan VC,Fritz NF,Tormey DC

    更新日期：1987-08-15 00:00:00

  • Differential regulation of cyclin-dependent kinase inhibitors in monolayer and spheroid cultures of tumorigenic and nontumorigenic fibroblasts.

    abstract：:The Ras proto-oncogene has been implicated in the in vivo development of tumors and in the in vitro transformation of cultured cell lines. In both of these conditions, Ras-mediated disruption of cell cycle-regulatory mechanisms leads to unregulated cellular proliferation, although the exact mechanisms by which Ras acc...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： LaRue KE,Bradbury EM,Freyer JP

    更新日期：1998-03-15 00:00:00

  • Increased methotrexate resistance and dhfr gene amplification as a consequence of induced Ha-ras expression in NIH 3T3 cells.

    abstract：:Oncogene activation and loss of tumor suppressor genes are known to play a role in tumor initiation as well as its progression. The potential roles of these genes in perturbation of genome stability has become a major interest. To better understand the relationship between expression of an oncogene and genetic instabi...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Wani MA,Xu X,Stambrook PJ

    更新日期：1994-05-01 00:00:00

  • In vivo induction of the lymphokine-activated killer phenomenon: interleukin 2-dependent human non-major histocompatibility complex-restricted cytotoxicity generated in vivo during administration of human recombinant interleukin 2.

    abstract：:The availability of purified human recombinant interleukin 2 (IL-2) has enabled clinical trials to test its in vivo effects. We report here the immunological effects of 7 consecutive days of IL-2 treatment given to 25 patients with cancer in a clinical Phase I study. Peripheral blood lymphocytes obtained from patients...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Hank JA,Kohler PC,Weil-Hillman G,Rosenthal N,Moore KH,Storer B,Minkoff D,Bradshaw J,Bechhofer R,Sondel PM

    更新日期：1988-04-01 00:00:00

  • Ionizing radiation inhibits chemotherapy-induced apoptosis in cultured glioma cells: implications for combined modality therapy.

    abstract：:Surgical resection followed by radiation therapy is the mainstay of treatment for glioblastoma multiforme (GBM), the most aggressive of the malignant gliomas. The poor clinical response of GBM and the intrinsic radiation resistance of this tumor type have prompted clinical investigations seeking to define the role of ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Yount GL,Haas-Kogan DA,Levine KS,Aldape KD,Israel MA

    更新日期：1998-09-01 00:00:00

  • In vitro purging of human rhabdomyosarcoma cells using 4-hydroperoxycyclophosphamide.

    abstract：:The outcome of patients with advanced stage rhabdomyosarcoma is extremely poor, with a disease-free survival of less than 20% at 3 years. Autologous bone marrow transplantation for patients with Clinical Group IV rhabdomyosarcoma may be an effective therapy. The bone marrow involvement diagnosed by light microscopy is...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Ozkaynak MF,Nolta J,Parkman R

    更新日期：1990-03-01 00:00:00

  • Differential regulation of cancer progression by CDK4/6 plays a central role in DNA replication and repair pathways.

    abstract：:Although the cyclin-dependent kinases CDK4 and CDK6 play fundamental roles in cancer, the specific pathways and downstream targets by which they exert their tumorigenic effects remain elusive. In this study, we uncover distinct and novel functions for these kinases in regulating tumor formation and metastatic coloniza...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-20-2121

    authors： Dai M,Boudreault J,Wang N,Poulet S,Daliah G,Yan G,Moamer A,Burgos SA,Sabri S,Ali S,Lebrun JJ

    更新日期：2020-12-28 00:00:00

  • Phase Ib Results of the Rational Combination of Selumetinib and Cyclosporin A in Advanced Solid Tumors with an Expansion Cohort in Metastatic Colorectal Cancer.

    abstract：:MEK inhibition is of interest in cancer drug development, but clinical activity in metastatic colorectal cancer (mCRC) has been limited. Preclinical studies demonstrated Wnt pathway overexpression in KRAS-mutant cell lines resistant to the MEK inhibitor, selumetinib. The combination of selumetinib and cyclosporin A, a...

    journal_title：Cancer research

    pub_type： 杂志文章,多中心研究

    doi：10.1158/0008-5472.CAN-18-0316

    authors： Krishnamurthy A,Dasari A,Noonan AM,Mehnert JM,Lockhart AC,Leong S,Capasso A,Stein MN,Sanoff HK,Lee JJ,Hansen A,Malhotra U,Rippke S,Gustafson DL,Pitts TM,Ellison K,Davis SL,Messersmith WA,Eckhardt SG,Lieu CH

    更新日期：2018-09-15 00:00:00

  • Comparisons of CYP2D messenger RNA splice variant profiles in human lung tumors and normal tissues.

    abstract：:Allelic variants of the CYP2D6 gene, a member of the cytochrome P450 gene superfamily, have been implicated in susceptibility to lung carcinogenesis. Human breast CYP2D6 and CYP2D7P (from a pseudogene) mRNAs were previously reported to be expressed as a series of splice variants. In this study, the expression of full-...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Huang Z,Fasco MJ,Spivack S,Kaminsky LS

    更新日期：1997-07-01 00:00:00

  • Inhibition of human malignant neuroblastoma cell DNA synthesis by lipoxygenase metabolites of arachidonic acid.

    abstract：:In vivo studies have shown that inhibitors of cyclooxygenase metabolism of arachidonic acid may diminish growth and metastasis of certain tumors. Because cyclooxygenase inhibition may increase the production of lipoxygenase products of arachidonic acid metabolism, we have investigated the effect of two such products, ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Werner EJ,Walenga RW,Dubowy RL,Boone S,Stuart MJ

    更新日期：1985-02-01 00:00:00

  • Subcellular distribution of inorganic pyrophosphatase activity in various normal and neoplastic cell types.

    abstract：:Inorganic pyrophosphatase (PPiase) activity was measured in cell fractions of rat, mouse, and human erythrocytes; normal rat liver; Novikoff hepatoma; Morris 3924A hepatoma; and mouse Ehrlich and Sarcoma 37 ascites tumors. Despite high intracellular activities, when precautions were taken to maintain cell integrity, o...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Shatton JB,Williams A,Weinhouse S

    更新日期：1983-08-01 00:00:00

  • Polymorphism in the N-acetyltransferase 1 (NAT1) polyadenylation signal: association of NAT1*10 allele with higher N-acetylation activity in bladder and colon tissue.

    abstract：:Exposures to carcinogens present in the diet, in cigarette smoke, or in the environment have been associated with increased risk of bladder and colorectal cancer. The aromatic amines and their metabolites, a class of carcinogen implicated in these exposures, can be N- or O-acetylated by the NAT1 and NAT2 enzymes. Acet...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Bell DA,Badawi AF,Lang NP,Ilett KF,Kadlubar FF,Hirvonen A

    更新日期：1995-11-15 00:00:00

  • Fas Ligand Deficiency Impairs Tumor Immunity by Promoting an Accumulation of Monocytic Myeloid-Derived Suppressor Cells.

    abstract：:The Fas receptor ligand FasL regulates immune cell levels by inducing apoptosis of Fas receptor-positive cells. Here, we studied the impact of host FasL on tumor development in mice. Genetically targeting FasL in naïve mice increased myeloid cell populations, but, in marked contrast, it reduced the levels of myeloid-d...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-14-1848

    authors： Peyvandi S,Buart S,Samah B,Vétizou M,Zhang Y,Durrieu L,Polrot M,Chouaib S,Benihoud K,Louache F,Karray S

    更新日期：2015-10-15 00:00:00

  • The plexin-A1 receptor activates vascular endothelial growth factor-receptor 2 and nuclear factor-kappaB to mediate survival and anchorage-independent growth of malignant mesothelioma cells.

    abstract：:The semaphorins and their receptors, the neuropilins and the plexins, are constituents of a complex regulatory system that controls axonal guidance. Moreover, many types of tumor cells express various members of semaphorins and receptors, but the biological activities within tumor mass and the signal transduction mech...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-08-3659

    authors： Catalano A,Lazzarini R,Di Nuzzo S,Orciari S,Procopio A

    更新日期：2009-02-15 00:00:00

  • Prognostic index for clinical Stage I cutaneous malignant melanoma.

    abstract：:Thirteen variables were evaluated for their significance in predicting the survival of 148 patients in a retrospective study with clinical Stage I cutaneous malignant melanoma. The variables studied were histological type, tumor thickness, level of invasion, mitotic activity, pigmentation type, existence of ulceration...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Hacene K,Le Doussal V,Brunet M,Lemoine F,Guerin P,Hebert H

    更新日期：1983-06-01 00:00:00

  • Main drug-metabolizing enzyme systems in human breast tumors and peritumoral tissues.

    abstract：:In an attempt to better understand breast tumors sensitivity or resistance to anticancer drugs, the main drug-metabolizing enzyme systems were evaluated in both breast tumors and their corresponding peritumoral tissues in 12 patients. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Albin N,Massaad L,Toussaint C,Mathieu MC,Morizet J,Parise O,Gouyette A,Chabot GG

    更新日期：1993-08-01 00:00:00

  • Stimulation of the nuclear uracil DNA glycosylase in proliferating human fibroblasts.

    abstract：:The cell cycle stimulation of individual species of the uracil DNA glycosylase was examined in WI-38 normal diploid fibroblasts. The nuclear uracil DNA glycosylase was induced as WI-38 cells traversed the cell cycle. In contrast, the specific activity of the mitochondrial glycosylase remained constant during cell prol...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Gupta PK,Sirover MA

    更新日期：1981-08-01 00:00:00

  • Dose response studies of carcinogenesis in rats by nitrosodiethylamine.

    abstract：:A dose-response study was conducted in Fischer rats with nitrosodiethylamine, which was administered in regulated amounts as a solution in drinking water. Groups of 20 female rats each received a different treatment, one group consisted of 12 animals; one of the groups was untreated. The concentrations of the solution...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Lijinsky W,Reuber MD,Riggs CW

    更新日期：1981-12-01 00:00:00

  • Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3.

    abstract：:Cytogenetic study of short-term cultures from 10 adipose tissue tumors (eight lipomas, one myxoid liposarcoma, and one mixed liposarcoma) have revealed clonal chromosome abnormalities in seven cases. In both malignant tumors, translocation (12;16) was the sole aberration, and in the mixed liposarcoma, the breakpoints ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Mrózek K,Karakousis CP,Bloomfield CD

    更新日期：1993-04-01 00:00:00

  • EBV is necessary for proliferation of dually infected primary effusion lymphoma cells.

    abstract：:Epstein Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are found together in approximately 80% of primary effusion lymphomas (PEL), but their contribution to these cancers is unclear. We found that dominant-negative derivatives of EBNA1 inhibited EBV-positive PEL cells from forming colonies. Those...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-08-0627

    authors： Mack AA,Sugden B

    更新日期：2008-09-01 00:00:00

  • Mechanism of cross-resistance to a camptothecin analogue (CPT-11) in a human ovarian cancer cell line selected by cisplatin.

    abstract：:We established a cisplatin-resistant human ovarian cancer cell line (HAC2/0.1) from the parent cell line (HAC2/P) by continuous exposure of HAC2/P to 0.1 microgram of cisplatin/ml. Drug sensitivity determined by colony assay revealed that HAC2/0.1 was 2.4 times as resistant to cisplatin as the parental cell line. HAC2...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Niimi S,Nakagawa K,Sugimoto Y,Nishio K,Fujiwara Y,Yokoyama S,Terashima Y,Saijo N

    更新日期：1992-01-15 00:00:00

  • Exchange of macromolecules between plasma and peritoneal cavity in ascites tumor-bearing, normal, and serotonin-injected mice.

    abstract：:Fluorescein-labeled dextrans (FITC-D) from 3 to 5000 kDa (Stokes' radii from 1 to 40 nm) were used to study influx from the plasma into the peritoneum and efflux from the peritoneal cavity into the plasma in normal and ascites tumor-bearing mice and in mice whose peritoneal vessels had been rendered hyperpermeable by ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Nagy JA,Herzberg KT,Masse EM,Zientara GP,Dvorak HF

    更新日期：1989-10-01 00:00:00

  • Carcinogenicity of hydroxylated alkylnitrosoureas and of nitrosooxazolidones by mouse skin painting and by gavage in rats.

    abstract：:The carcinogenic effectiveness of a number of nitrosoalkylamides related to nitrosoethylurea and nitroso-n-propylurea has been compared by topical application to Swiss mice and by intragastric administration to F344 rats. Nitrosohydroxyethylurea and the related cyclic nitrosamide, nitrosooxazolidone, were as potent as...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Lijinsky W,Reuber MD

    更新日期：1983-01-01 00:00:00

  • Adeno-associated virus 2-mediated antiangiogenic cancer gene therapy: long-term efficacy of a vector encoding angiostatin and endostatin over vectors encoding a single factor.

    abstract：:Angiogenesis is characteristic of solid tumor growth and a surrogate marker for metastasis in many human cancers. Inhibition of tumor angiogenesis using antiangiogenic drugs and gene transfer approaches has suggested the potential of this form of therapy in controlling tumor growth. However, for long-term tumor-free s...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.can-03-1786

    authors： Ponnazhagan S,Mahendra G,Kumar S,Shaw DR,Stockard CR,Grizzle WE,Meleth S

    更新日期：2004-03-01 00:00:00

  • Transformation nonresponsive cells owe their resistance to lack of p65/nuclear factor-kappaB activation.

    abstract：:Clonal variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to tumor promoter-induced neoplastic transformation exhibit differential activator protein-1 (AP-1) response. Transactivation of AP-1 appears to be necessary but not sufficient to promote transformation in JB6 cells. I...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Hsu TC,Nair R,Tulsian P,Camalier CE,Hegamyer GA,Young MR,Colburn NH

    更新日期：2001-05-15 00:00:00

  • Comparative morphometric study of tumor vasculature in human squamous cell carcinomas and their xenotransplants in athymic nude mice.

    abstract：:When human tumor xenotransplants into nude mice are used as experimental models, it is important to know whether their microvascular anatomy is rather host or tumor specific. Therefore a morphometric comparison of the vascular network in human squamous cell carcinomas and their xenotransplants was carried out. Biopsie...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Lauk S,Zietman A,Skates S,Fabian R,Suit HD

    更新日期：1989-08-15 00:00:00