Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation.

Abstract:

:Internal tandem duplication (ITD) of the juxtamembrane region of FMS-like tyrosine kinase-3 (FLT3) receptor is a common type of mutation in adult acute myeloid leukemia (AML), and patient response to FLT3 inhibitors appears to be transient due to the emergence of drug resistance. We established two sorafenib-resistant cell lines carrying FLT3/ITD mutations, including the murine BaF3/ITD-R and human MV4-11-R cell lines. Gene expression profile analysis of the resistant and parental cells suggests that the highest ranked molecular and cellular functions of the differentially expressed genes are related to mitochondrial dysfunction. Both murine and human resistant cell lines display a longer doubling time, along with a significant inhibition of mitochondrial respiratory chain activity and substantial upregulation of glycolysis. The sorafenib-resistant cells exhibit increased expression of a majority of glycolytic enzymes, including hexokinase 2, which is also highly expressed in the mitochondrial fraction and is associated with resistance to apoptotic cell death. The sorafenib-resistant cells are collaterally sensitive to a number of glycolytic inhibitors including 2-deoxyglucose and 3-bromopyruvate propylester. Our study reveals a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Huang A,Ju HQ,Liu K,Zhan G,Liu D,Wen S,Garcia-Manero G,Huang P,Hu Y

doi

10.1016/j.canlet.2016.04.040

subject

Has Abstract

pub_date

2016-07-28 00:00:00

pages

149-57

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(16)30276-2

journal_volume

377

pub_type

杂志文章
  • Insulin-like growth factor binding protein-3 inhibits migration of endometrial cancer cells.

    abstract::Cell migration and invasion leading to metastasis is a major cause of death from endometrial cancer (EC). We have shown that the rate of EC cell migration is inversely related to the level of insulin-like growth factor protein-3 (IGFBP-3). Down-regulation of IGFBP-3 by siRNA in EC cells accelerated migration without a...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2011.11.011

    authors: Gribben L,Baxter RC,Marsh DJ

    更新日期:2012-04-01 00:00:00

  • Chemopreventive properties of the ethanol extract of chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells.

    abstract::Much of the interest on the chemopreventive properties of licorice has been focused on the plant genius Glycyrrhiza glabra. In this study the ethanol extract of Chinese licorice root, Glycyrrhiza uralensis (G. uralensis) was investigated for its estrogenic effect and the ability to inhibit cell proliferation in the MC...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2004.12.038

    authors: Jo EH,Kim SH,Ra JC,Kim SR,Cho SD,Jung JW,Yang SR,Park JS,Hwang JW,Aruoma OI,Kim TY,Lee YS,Kang KS

    更新日期:2005-12-18 00:00:00

  • Comparative carcinogenicity in F344 rats and Syrian golden hamsters of N'-nitrosonornicotine and N'-nitrosonornicotine-1-N-oxide.

    abstract::N'-Nitrosonornicotine (NNN) or N'-nitrosonornicotine-1-N-oxide (NNN-1-N-oxide), one of its metabolites, was added to the drinking water (0.012% for 36 weeks) of groups of male and female F344 rats or to the drinking water (0.016% for 31 weeks) of groups of male and female Syrian golden hamsters. All rats treated with ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(83)90032-0

    authors: Hecht SS,Young R,Maeura Y

    更新日期:1983-10-01 00:00:00

  • Enhanced thermal response of a rat sarcoma by Corynebacterium parvum.

    abstract::Corynebacterium parvum was investigated in the response of rat Mc7 sarcoma to local waterbath hyperthermia. Heat treatment of 1-1.5 cm3 foot tumors at 43 degrees C for 2 h resulted in complete regression of 71% of the tumors. The Mc7 cure was reduced to 31% when the tumors were heated at 43 degrees C for 1.5 h. C. par...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(85)90031-x

    authors: Shah SA

    更新日期:1985-03-01 00:00:00

  • Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to Sunitinib.

    abstract::Resistance to chemotherapy is a challenging problem for treatment of cancer patients and autophagy has been shown to mediate development of resistance. In this study we systematically screened a library of 306 known anti-cancer drugs for their ability to induce autophagy using a cell-based assay. 114 of the drugs were...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2018.07.028

    authors: Dyczynski M,Yu Y,Otrocka M,Parpal S,Braga T,Henley AB,Zazzi H,Lerner M,Wennerberg K,Viklund J,Martinsson J,Grandér D,De Milito A,Pokrovskaja Tamm K

    更新日期:2018-10-28 00:00:00

  • Magnetic polyethyleneimine (PEI) microcapsules as retrievable traps for carcinogen electrophiles formed in the gastrointestinal tract.

    abstract::Semi-permeable magnetic microcapsules containing polyethyleneimine (PEI) have been developed as retrievable carcinogen traps. In vitro, the soluble core PEI and membrane both bound reactive substances of limited aqueous stability, such as from [14C]N-methyl-N-nitrosourea ([14C]NMU), and aqueous stable dyes of molecula...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(87)90101-7

    authors: Povey AC,Bartsch H,O'Neill IK

    更新日期:1987-07-01 00:00:00

  • Is reduction of tumor burden sufficient for the 21st century?

    abstract::Currently, animal models are used to test the efficacy of tumor treatment. A significant reduction of tumor mass is lauded as great improvement. As we begin the 21st century, one wonders if this is sufficient and acceptable for cancer treatment. Although the presence of cancer stem cell (CSCs) is not a new phenomenon,...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2014.03.002

    authors: Nahas G,Bliss SA,Sinha G,Ganta T,Greco SJ,Rameshwar P

    更新日期:2015-01-28 00:00:00

  • A novel homozygous deletion at chromosomal band 6q27 in an ovarian cancer cell line delineates the position of a putative tumor suppressor gene.

    abstract::Chromosomal band 6q27 is believed to contain a tumor suppressor gene important in the development of several cancer types, including ovarian cancer. However, repeated efforts to identify a tumor suppressor gene in this region have been unsuccessful. Because homozygous deletions have been useful in the positional cloni...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(01)00677-2

    authors: Lin H,Morin PJ

    更新日期:2001-11-08 00:00:00

  • Induction of differentiation of human promyelocytic leukemia cells (HL-60) by arginase.

    abstract::Human promyelocytic leukemia cells (HL-60) were found to be induced by dimethylsulfoxide and several other compounds to phagocytize, reduce NBT dye, and change into forms that were morphologically similar to granulocytes and macrophages. Arginase also induced these differentiation-associated properties of the cells. T...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(80)90044-0

    authors: Honma Y,Fujita Y,Okabe-Kado J,Kasukabe T,Hozumi M

    更新日期:1980-10-01 00:00:00

  • Toxoplasma gondii infection in cancer patients: prevalence, risk factors, genotypes and association with clinical diagnosis.

    abstract::Prevalence of human infection with Toxoplasma gondii has been increasing in China due to the increasing number of cats. However, little is known of the epidemiology of T. gondii infection in different cancer patient groups. Thus, a case-control study of 900 cancer patients and 900 controls was conducted to detect anti...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2015.01.036

    authors: Cong W,Liu GH,Meng QF,Dong W,Qin SY,Zhang FK,Zhang XY,Wang XY,Qian AD,Zhu XQ

    更新日期:2015-04-10 00:00:00

  • The soluble EP2 receptor FuEP2/Ex2 suppresses endometrial cancer cell growth in an orthotopic xenograft model in nude mice.

    abstract::Endometrial cancer is one of the most common gynecologic malignancies and many factors influence in its growth and development. As in many other types of cancer, prostaglandin E(2) (PGE(2)) is thought to be an accelerator of cell proliferation and endometrial cancer progression. In this study, we examined the effect o...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2011.02.033

    authors: Takahashi T,Ogawa H,Izumi K,Uehara H

    更新日期:2011-07-01 00:00:00

  • Effect of magnesium hydroxide on methylazoxymethanol acetate-induced epithelial proliferation in the large bowels of rats.

    abstract::The effect of magnesium hydroxide on the epithelial proliferation of the large bowel was examined using rats given methylazoxymethanol (MAM) acetate. Dietary administration of magnesium hydroxide at 250, 500, 1000 or 2000 ppm. for 1, 3 or 5 weeks did not influence the cell cycle of the cryptal cells of the large bowel...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(92)90196-3

    authors: Mori H,Morishita Y,Mori Y,Yoshimi N,Sugie S,Tanaka T

    更新日期:1992-02-14 00:00:00

  • Nucleostemin/GNL3 promotes nucleolar polyubiquitylation of p27kip1 to drive hepatocellular carcinoma progression.

    abstract::p27kip, as a cyclin dependent kinase inhibitor (CDKI), plays a pivotal role in the regulation of cell cycle progression and hepatocarcinogenesis. Herein, we revealed that p27 exhibited apparent nucleolar distribution and interacted with nucleolar protein nucleostemin (NS) in Hepatocellular carcinoma (HCC) cells. Furth...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2016.12.008

    authors: Hu B,Hua L,Ni W,Wu M,Yan D,Chen Y,Lu C,Chen B,Wan C

    更新日期:2017-03-01 00:00:00

  • Viral therapy for pancreatic cancer: tackle the bad guys with poison.

    abstract::Pancreatic cancer is one of the most devastating diseases with very poor prognosis. Only a small proportion is curable by surgical resection, whilst standard chemotherapy for patients with advanced disease has only modest effect with substantial toxicity. Therefore, there is an urgent need for the development of novel...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2013.01.035

    authors: Xu C,Li H,Su C,Li Z

    更新日期:2013-06-01 00:00:00

  • Macrophage migration inhibitory factor promotes breast cancer metastasis via activation of HMGB1/TLR4/NF kappa B axis.

    abstract::Macrophage migration inhibitory factor (MIF) is up-regulated in diverse solid tumors and acts as the critical link between immune response and tumorigenesis. In this study, we demonstrated that MIF overexpression promoted migration of breast cancer cells by elevating TLR4 expression. Further investigation evidenced th...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2016.02.005

    authors: Lv W,Chen N,Lin Y,Ma H,Ruan Y,Li Z,Li X,Pan X,Tian X

    更新日期:2016-06-01 00:00:00

  • Exposure to low dose ionising radiation: Molecular and clinical consequences.

    abstract::This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HR...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2013.12.015

    authors: Martin LM,Marples B,Lynch TH,Hollywood D,Marignol L

    更新日期:2014-07-10 00:00:00

  • The inhibitory action of BOF-A2, a 5-fluorouracil derivative, on squamous cell carcinoma.

    abstract::Inactivation of antineoplastics is a serious problem in cancer therapy, and prevention of the inactivation is a surpassing strategy for enhancement of their therapeutic effects. BOF-A2, which contains both EM-FU, a masked form of 5-fluorouracil (5-FU), and CNDP, an inhibitor of 5-FU degradation, was developed with thi...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(98)00330-9

    authors: Yoneda K,Yamamoto T,Ueta E,Osaki T

    更新日期:1999-03-22 00:00:00

  • Autophagy regulation as a promising approach for improving cancer immunotherapy.

    abstract::Autophagy plays a critical role in intracellular metabolism and maintaining cellular homeostasis. Certain tumor cells present a higher basal autophagy rate and autophagy inhibition can lead to impaired metabolic dysfunction in autophagy-dependent tumor cells. Autophagy status in immune cells dictates their fate and re...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2020.01.034

    authors: Ishimwe N,Zhang W,Qian J,Zhang Y,Wen L

    更新日期:2020-04-10 00:00:00

  • Serum evaluation of basic fibroblast growth factor in cervical cancer patients.

    abstract::We present the data of 105 serum samples from 20 patients suffering from cervical cancer. Mean serum levels of basic fibroblast growth factor (bFGF) in patients with or without tumor present were 31.3 +/- 32.1 (minimum 0, maximum 156.7) pg/ml and 4.8 +/- 6.8 (minimum 0, maximum 29.6) pg/ml, respectively (P = 0.0001). ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(95)03853-o

    authors: Sliutz G,Tempfer C,Obermair A,Reinthaller A,Gitsch G,Kainz C

    更新日期:1995-08-01 00:00:00

  • Cancer omics: from regulatory networks to clinical outcomes.

    abstract::Current limitation in cancer genomic studies is a lack of the integration of various omics data generated through next generation sequencing technologies, as well as a lack of the sounding and comprehensive epigenomic and genomic information about a particular cancer cell type. In this review, we will discuss main asp...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2012.11.033

    authors: Tang B,Hsu PY,Huang TH,Jin VX

    更新日期:2013-11-01 00:00:00

  • Use of a tetrazolium based colorimetric assay in assessing photoradiation therapy in vitro.

    abstract::The suitability of a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] assay to the determination of cell viability following photoradiation therapy (PRT) of human breast and melanoma cell lines has been examined. Results have been shown to correlate with those obtained using a clonogen...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(88)90293-5

    authors: McHale AP,McHale L

    更新日期:1988-08-30 00:00:00

  • Altered extracellular ATP, ADP and AMP catabolism in glioma cell lines.

    abstract::In order to characterize the enzymes involved in the purine nucleotide catabolism as indicators of invasiveness and aggressiveness of malignant gliomas, the degradation of extracellular nucleotides by five different glioma cell lines was investigated and compared with primary astrocytes. Rapid hydrolysis of extracellu...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(03)00308-2

    authors: Wink MR,Lenz G,Braganhol E,Tamajusuku AS,Schwartsmann G,Sarkis JJ,Battastini AM

    更新日期:2003-08-20 00:00:00

  • Inhibitory effect of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel synthesized retinoid, on azoxymethane-induced intestinal carcinogenesis in rats.

    abstract::Modifying effects of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel synthesized retinoid (KYN-54), on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of ninety male F344 rats, 6 weeks old, were divided into 4 groups. Group 1 (20 rats) was fed a diet containing KYN-5...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(92)90220-p

    authors: Mori H,Yoshimi N,Sugie S,Tanaka T,Morishita Y,Jinlong G,Tamai Y,Torihara M,Yamahara J

    更新日期:1992-09-30 00:00:00

  • Lectin reactivity of murine fibrosarcoma lines with a different metastatic potential.

    abstract::Lectins are suitable tools for investigating the glycoconjugate characteristics of metastatic cells. In the present study, we investigated whether there were differences between high metastatic T3 cells and a low metastatic isolate in their reactivities to several lectins specific for galactosyl and sialyl groups. Ana...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(91)90177-j

    authors: Mannori G,Mugnai G,Ruggieri S

    更新日期:1991-08-01 00:00:00

  • Pre-microRNA variants predict HPV16-positive tumors and survival in patients with squamous cell carcinoma of the oropharynx.

    abstract::To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2012.11.048

    authors: Guan X,Sturgis EM,Song X,Liu Z,El-Naggar AK,Wei Q,Li G

    更新日期:2013-04-28 00:00:00

  • Reactive oxygen species-mediated kinase activation by dihydrotanshinone in tanshinones-induced apoptosis in HepG2 cells.

    abstract::The role of reactive oxygen species (ROS) and p38 mitogen-activated protein kinases (MAPK) in tanshinones-induced apoptosis was investigated in HepG2 cells in this study. The major tanshinones (cryptotanshinone, dihydrotanshinone, tanshinone I, tanshinone IIA), isolated from Salvia miltiorrhiza, inhibit cell growth an...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2009.04.040

    authors: Lee WY,Liu KW,Yeung JH

    更新日期:2009-11-18 00:00:00

  • Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma: Current status.

    abstract::Radiofrequency ablation (RFA) is widely accepted as a first-line interventional oncology approach for hepatocellular carcinoma (HCC) and has the advantages of high treatment efficacy and low complication risk. Local control rates equivalent to hepatic resection can be reached by RFA alone when treating small HCCs (<2 ...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2015.09.020

    authors: Chen L,Sun J,Yang X

    更新日期:2016-01-01 00:00:00

  • Vasohibin 2 promotes human luminal breast cancer angiogenesis in a non-paracrine manner via transcriptional activation of fibroblast growth factor 2.

    abstract::Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunoso...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2016.09.031

    authors: Tu M,Lu C,Lv N,Wei J,Lu Z,Xi C,Chen J,Guo F,Jiang K,Li Q,Wu J,Song G,Wang S,Gao W,Miao Y

    更新日期:2016-12-28 00:00:00

  • AXIN1 and AXIN2 variants in gastrointestinal cancers.

    abstract::Mutations in the APC (adenomatous polyposis coli) gene, which encodes a multi-functional protein with a well-defined role in the canonical Wnt pathway, underlie familial adenomatous polypsosis, a rare, inherited form of colorectal cancer (CRC) and contribute to the majority of sporadic CRCs. However, not all sporadic ...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2014.09.018

    authors: Mazzoni SM,Fearon ER

    更新日期:2014-12-01 00:00:00

  • Heterogeneous pattern of gene expression in cloned cell lines established from a rat transplantable osteosarcoma lung metastatic nodule.

    abstract::We have established three cloned cell lines (COS1NR, COS2NR and COS4NR) from the lung metastatic nodule of a highly metastatic variant of rat transplantable osteosarcoma, C-SLM. All three clones shared the same morphological characteristics and tumorigenicity, but their growth rates in vitro and metastatic ability in ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(98)00048-2

    authors: Honoki K,Mori T,Tsutsumi M,Tsujiuchi T,Kido A,Morishita T,Miyauchi Y,Dohi Y,Mii Y,Tamai S,Konishi Y

    更新日期:1998-05-15 00:00:00