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NCI-H460

RRID:CVCL_0459

Organism

Homo sapiens

Comments

Part of: Cancer Cell Line Encyclopedia (CCLE) project. Part of: COSMIC cell lines project. Part of: EGFR genetic alteration cell panel (ATCC TCP-1027). Part of: JFCR39 cancer cell line panel. Part of: KuDOS 95 cell line panel. Part of: MD Anderson Cell Lines Project. Part of: NCI-60 cancer cell line panel. Doubling time: 33 hours (in RPMI 1640 + 10% FBS), 60 hours (in ACL-3), 42 hours (in ACL-3 + BSA) (PubMed=3940644); 17.8 hours (NCI-DTP); ~23 hours (DSMZ). HLA typing: A*24,68; B*35,51; C*03,15; DQB1*03:01:01,05:01:01; DRB1*01,04 (PubMed=15748285). Microsatellite instability: Stable (MSS) (Sanger). Sequence variation: Homozygous for KRAS p.Gln61His (c.183A>T) (PubMed=12068308; PubMed=12794755; PubMed=17088437). Sequence variation: Heterozygous for PIK3CA p.Glu545Lys (c.1633G>A) (PubMed=17088437). Sequence variation: Homozygous for STK11 p.Gln37Ter (c.109C>T) (PubMed=17088437). Sequence variation: Has no TP53 mutation (PubMed=1311061; PubMed=15900046). Omics: Array-based CGH. Omics: CNV analysis. Omics: Deep exome analysis. Omics: Deep phosphoproteome analysis. Omics: Deep proteome analysis. Omics: Deep RNAseq analysis. Omics: Fluorescence phenotype profiling. Omics: lncRNA expression profiling. Omics: Metabolome analysis. Omics: Protein expression by reverse-phase protein arrays. Omics: SNP array analysis. Omics: Transcriptome analysis. Genome ancestry: African=0%; Native American=0%; East Asian, North=1.96%; East Asian, South=0%; South Asian=0.15%; European, North=65.65%; European, South=32.24% (PubMed=30894373). Derived from metastatic site: Pleural effusion. DT Created: 04-04-12; Last updated: 06-09-19; Version: 32

Proper Citation

KCB Cat# KCB 2010102YJ, RRID:CVCL_0459

Category

Cancer cell line DT Created: 04-04-12; Last updated: 06-09-19; Version: 32

Sex

DT Created: 04-04-12; Last updated: 06-09-19; Version: 32

Synonyms

NCI.H460, H460, H-460, NCIH460, NCI-HUT-460, NCI-460 DT Created: 04-04-12, Last updated: 06-09-19, Version: 32

Vendor

KCB

Cat Num

KCB 2010102YJ

Cross References

BTO; BTO:0002207 CLO; CLO_0003601 CLO; CLO_0008089 EFO; EFO_0003044 MCCL; MCC:0000356 CLDB; cl1548 4DN; 4DNSRZBU6PZA AddexBio; C0016003/39 ArrayExpress; E-MTAB-2706 ArrayExpress; E-MTAB-2770 ATCC; HTB-177 BCRC; 60373 BioSample; SAMN03471184 BioSample; SAMN10987808 CCLE; NCIH460_LUNG CCLV; CCLV-RIE 0962 CCRID; 3111C0001CCC000355 CCRID; 3111C0002000000086 CCRID; 3131C0001000700039 CCRID; 3131C0001000700205 CCRID; 3142C0001000001714 CCTCC; GDC0109 Cell_Model_Passport; SIDM00144 CGH-DB; 199-1 CGH-DB; 9186-4 ChEMBL-Cells; CHEMBL3307677 ChEMBL-Targets; CHEMBL396 Cosmic; 722064 Cosmic; 724876 Cosmic; 755469 Cosmic; 844595 Cosmic; 875852 Cosmic; 877263 Cosmic; 877407 Cosmic; 897508 Cosmic; 905943 Cosmic; 911996 Cosmic; 931371 Cosmic; 947356 Cosmic; 980964 Cosmic; 1006534 Cosmic; 1017826 Cosmic; 1028956 Cosmic; 1032436 Cosmic; 1044245 Cosmic; 1047102 Cosmic; 1089231 Cosmic; 1092621 Cosmic; 1146917 Cosmic; 1154605 Cosmic; 1152502 Cosmic; 1188592 Cosmic; 1219077 Cosmic; 1239922 Cosmic; 1305349 Cosmic; 1312334 Cosmic; 1434967 Cosmic; 1436013 Cosmic; 1477420 Cosmic; 1802310 Cosmic; 1870275 Cosmic; 1945869 Cosmic; 1995579 Cosmic; 1998463 Cosmic; 2042872 Cosmic; 2058650 Cosmic; 2125199 Cosmic; 2433756 Cosmic; 2560230 Cosmic; 2630413 Cosmic; 2664114 Cosmic-CLP; 905943 DepMap; ACH-000463 DSMZ; ACC-737 ENCODE; ENCBS398KLJ ENCODE; ENCBS446PPO ENCODE; ENCBS460OUE ENCODE; ENCBS514AAA ENCODE; ENCBS515AAA ENCODE; ENCBS641PGO ENCODE; ENCBS686KKP ENCODE; ENCBS798ZFS ENCODE; ENCBS814QPR GDSC; 905943 GEO; GSM2152 GEO; GSM50216 GEO; GSM50279 GEO; GSM206493 GEO; GSM253335 GEO; GSM274737 GEO; GSM274738 GEO; GSM385522 GEO; GSM385533 GEO; GSM434334 GEO; GSM513936 GEO; GSM514322 GEO; GSM750809 GEO; GSM784193 GEO; GSM794288 GEO; GSM799343 GEO; GSM799406 GEO; GSM827469 GEO; GSM844652 GEO; GSM844651 GEO; GSM847076 GEO; GSM887430 GEO; GSM888510 GEO; GSM1153414 GEO; GSM1181352 GEO; GSM1181361 GEO; GSM1374746 GEO; GSM1374747 GEO; GSM1374748 GEO; GSM1557134 GEO; GSM2124676 IARC_TP53; 21083 IGRhCellID; NCI-H460%20GEO IZSLER; BS TCL 197 KCB; KCB 2010102YJ KCLB; 30177 LiGeA; CCLE_338 LINCS_LDP; LCL-1784 Lonza; 728 NCI-DTP; NCI-H460 PharmacoDB; NCIH460_1114_2019 PRIDE; PXD005940 PRIDE; PXD005942 SKY/M-FISH/CGH; 2798 Wikidata; Q54908057 DT Created: 04-04-12; Last updated: 06-09-19; Version: 32

Hierarchy

DT Created: 04-04-12; Last updated: 06-09-19; Version: 32

Originate from Same Individual

DT Created: 04-04-12; Last updated: 06-09-19; Version: 32

Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression.

  • Park MH
  • Theranostics
  • 2018 Jun 11

Literature context:


Abstract:

Some epidemiological studies suggest an inverse correlation between cancer incidence and Alzheimer's disease (AD). In this study, we demonstrated experimental evidences for this inverse relationship. In the co-expression network analysis using the microarray data and GEO profile of gene expression omnibus data analysis, we showed that the expression of peroxiredoxin 6 (PRDX6), a tumor promoting protein was significantly increased in human squamous lung cancer, but decreased in mutant presenilin 2 (PS2) containing AD patient. We also found in animal model that mutant PS2 transgenic mice displayed a reduced incidence of spontaneous and carcinogen-induced lung tumor development compared to wildtype transgenic mice. Agreed with network and GEO profile study, we also revealed that significantly reduced expression of PRDX6 and activity of iPLA2 in these animal models. PS2 mutations increased their interaction with PRDX6, thereby increasing iPLA2 cleavage via increased γ-secretase leading to loss of PRDX6 activity. However, knockdown or inhibition of γ-secretase abolished the inhibitory effect of mutant PSs. Moreover, PS2 mutant skin fibroblasts derived from patients with AD showed diminished iPLA2 activity by the elevated γ-secretase activity. Thus, the present data suggest that PS2 mutations suppress lung tumor development by inhibiting the iPLA2 activity of PRDX6 via a γ-secretase cleavage mechanism and may explain the inverse relationship between cancer and AD incidence.

The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma.

  • Momcilovic M
  • Cancer Cell
  • 2018 May 14

Literature context:


Abstract:

Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.

Funding information:
  • NIAMS NIH HHS - R01 AR061567(United States)

SPIN1 promotes tumorigenesis by blocking the uL18 (universal large ribosomal subunit protein 18)-MDM2-p53 pathway in human cancer.

  • Fang Z
  • Elife
  • 2018 Mar 16

Literature context:


Abstract:

Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here, we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity toward p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 may be attributed to its negative regulation of uL18, leading to p53 inactivation.

Funding information:
  • National Institutes of Health - 2G12MD007595()
  • National Institutes of Health - R01CA095441()
  • National Institutes of Health - R01CA127724()
  • National Institutes of Health - R01CA172468()
  • National Institutes of Health - R21 CA201889()
  • National Institutes of Health - R21CA190775()
  • NCI NIH HHS - CA89194(United States)

LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer.

  • Tavazoie MF
  • Cell
  • 2018 Feb 8

Literature context:


Abstract:

Therapeutic harnessing of adaptive immunity via checkpoint inhibition has transformed the treatment of many cancers. Despite unprecedented long-term responses, most patients do not respond to these therapies. Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and pharmacological approaches, we uncovered a pathway governing MDSC abundance in multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients treated in a first-in-human dose escalation phase 1 trial. MDSC depletion was associated with activation of cytotoxic T lymphocyte (CTL) responses in mice and patients. The LXR transcriptional target ApoE mediated these effects in mice, where LXR/ApoE activation therapy elicited robust anti-tumor responses and also enhanced T cell activation during various immune-based therapies. We implicate the LXR/ApoE axis in the regulation of innate immune suppression and as a target for enhancing the efficacy of cancer immunotherapy in patients.

Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer.

  • Topper MJ
  • Cell
  • 2017 Nov 30

Literature context:


Abstract:

Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction. This is accompanied by suppression of MYC signaling and an increase in the T cell chemoattractant CCL5. Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes. Key correlative science metrics emerge for an upcoming clinical trial, testing enhancement of immune checkpoint therapy for NSCLC.

Funding information:
  • NCI NIH HHS - P30 CA006973()
  • NCI NIH HHS - R01 CA121113()
  • NCI NIH HHS - R01 CA166348()
  • NIDA NIH HHS - R01 DA007427(United States)

Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer.

  • Bar-Peled L
  • Cell
  • 2017 Oct 19

Literature context:


Abstract:

The transcription factor NRF2 is a master regulator of the cellular antioxidant response, and it is often genetically activated in non-small-cell lung cancers (NSCLCs) by, for instance, mutations in the negative regulator KEAP1. While direct pharmacological inhibition of NRF2 has proven challenging, its aberrant activation rewires biochemical networks in cancer cells that may create special vulnerabilities. Here, we use chemical proteomics to map druggable proteins that are selectively expressed in KEAP1-mutant NSCLC cells. Principal among these is NR0B1, an atypical orphan nuclear receptor that we show engages in a multimeric protein complex to regulate the transcriptional output of KEAP1-mutant NSCLC cells. We further identify small molecules that covalently target a conserved cysteine within the NR0B1 protein interaction domain, and we demonstrate that these compounds disrupt NR0B1 complexes and impair the anchorage-independent growth of KEAP1-mutant cancer cells. Our findings designate NR0B1 as a druggable transcriptional regulator that supports NRF2-dependent lung cancers.

BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment.

  • Winter GE
  • Mol. Cell
  • 2017 Jul 6

Literature context:


Abstract:

Processive elongation of RNA Polymerase II from a proximal promoter paused state is a rate-limiting event in human gene control. A small number of regulatory factors influence transcription elongation on a global scale. Prior research using small-molecule BET bromodomain inhibitors, such as JQ1, linked BRD4 to context-specific elongation at a limited number of genes associated with massive enhancer regions. Here, the mechanistic characterization of an optimized chemical degrader of BET bromodomain proteins, dBET6, led to the unexpected identification of BET proteins as master regulators of global transcription elongation. In contrast to the selective effect of bromodomain inhibition on transcription, BET degradation prompts a collapse of global elongation that phenocopies CDK9 inhibition. Notably, BRD4 loss does not directly affect CDK9 localization. These studies, performed in translational models of T cell leukemia, establish a mechanism-based rationale for the development of BET bromodomain degradation as cancer therapy.

Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy.

  • Hu M
  • Mol. Cell
  • 2017 Apr 6

Literature context:


Abstract:

Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling. The interaction is mediated by an LxxLL motif in TRAF2 and results not only in the inhibition of TRAF2 ubiquitination but also in Lys63-linked Nur77 ubiquitination. Under inflammatory conditions, ubiquitinated Nur77 resides at mitochondria, rendering them sensitive to autophagy, an event involving Nur77 interaction with p62/SQSTM1. Together, our results identify Nur77 as a critical intracellular target for celastrol and unravel a mechanism of Nur77-dependent clearance of inflamed mitochondria to alleviate inflammation.

Funding information:
  • NIDA NIH HHS - 1P30 DA035756-01(United States)

MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor cells.

  • Bridges KA
  • Oncotarget
  • 2016 Nov 1

Literature context:


Abstract:

Radiotherapy is commonly used to treat a variety of solid tumors but improvements in the therapeutic ratio are sorely needed. The aim of this study was to assess the Chk1 kinase inhibitor, MK-8776, for its ability to radiosensitize human tumor cells. Cells derived from NSCLC and HNSCC cancers were tested for radiosensitization by MK-8776. The ability of MK-8776 to abrogate the radiation-induced G2 block was determined using flow cytometry. Effects on repair of radiation-induced DNA double strand breaks (DSBs) were determined on the basis of rad51, γ-H2AX and 53BP1 foci. Clonogenic survival analyses indicated that MK-8776 radiosensitized p53-defective tumor cells but not lines with wild-type p53. Abrogation of the G2 block was evident in both p53-defective cells and p53 wild-type lines indicating no correlation with radiosensitization. However, only p53-defective cells entered mitosis harboring unrepaired DSBs. MK-8776 appeared to inhibit repair of radiation-induced DSBs at early times after irradiation. A comparison of MK-8776 to the wee1 inhibitor, MK-1775, suggested both similarities and differences in their activities. In conclusion, MK-8776 radiosensitizes tumor cells by mechanisms that include abrogation of the G2 block and inhibition of DSB repair. Our findings support the clinical evaluation of MK-8776 in combination with radiation.

Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation.

  • Cao B
  • Elife
  • 2016 Jul 7

Literature context:


Abstract:

Increasing evidence highlights the important roles of microRNAs in mediating p53's tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes. Knockdown of p53 reversed these effects. Also, overexpression of miR-139-5p decreased PDE4D levels and increased cellular cAMP levels, leading to BIM-mediated cell growth arrest. Furthermore, our analysis of human colorectal tumor specimens revealed significant inverse correlation between the expression of miR-139-5p and that of PDE4D. Finally, overexpression of miR-139-5p suppressed the growth of xenograft tumors, accompanied by decrease in PDE4D and increase in BIM. These results demonstrate that p53 inactivates oncogenic PDE4D by inducing the expression of miR-139-5p.