Kit-activating mutations cooperate with Spi-1/PU.1 overexpression to promote tumorigenic progression during erythroleukemia in mice.

Abstract:

:The erythroleukemia developed by spi-1/PU.1 transgenic mice is a multistage process characterized by an early arrest of the proerythroblast differentiation followed later on by malignant transformation. Herein, we report the presence of acquired mutations in the SCF receptor gene (Kit) in 86% of tumors isolated during the late stage of the disease. Kit mutations affect codon 814 or 818. Ectopic expression of Kit mutants in nonmalignant proerythroblasts confers erythropoietin independence and tumorigenicity to cells. Using PP1, PP2, and imatinib mesylate, we show that Kit mutants are responsible for the autonomous expansion of malignant cells via Erk1/2 and PI3K/Akt activations. These findings represent a proof of principle for oncogenic cooperativity between one proliferative and one differentiation blocking event for the development of an overt leukemia.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Kosmider O,Denis N,Lacout C,Vainchenker W,Dubreuil P,Moreau-Gachelin F

doi

10.1016/j.ccr.2005.11.009

keywords:

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

467-78

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(05)00365-X

journal_volume

8

pub_type

杂志文章
  • Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway.

    abstract::Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in meta...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/s1535-6108(04)00081-9

    authors: Bao S,Ouyang G,Bai X,Huang Z,Ma C,Liu M,Shao R,Anderson RM,Rich JN,Wang XF

    更新日期:2004-04-01 00:00:00

  • No need for constant help: human IgG2 antibodies have an autonomous agonistic activity for immunotherapy of cancer.

    abstract::Agonistic antibodies specific for members of the tumor necrosis factor receptor protein family hold great promise for immunotherapy of cancer. In this issue of Cancer Cell, White and colleagues provide evidence that the human IgG2 subclass may represent a superior backbone for the use of these antibodies in human ther...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2014.12.010

    authors: Lux A,Nimmerjahn F

    更新日期:2015-01-12 00:00:00

  • Crosstown Traffic: Lymphodepleting Chemotherapy Drives CAR T Cells.

    abstract::CAR-engineered T cell immunotherapy has proven transformative in selected hematological malignancies. However, solid tumors largely remain impervious to these approaches. In addressing this challenge, Srivastava et al. in this issue demonstrate that oxaliplatin-based lymphodepleting chemotherapy promotes enhanced CAR ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2020.12.019

    authors: Davies DM,Maher J

    更新日期:2020-12-30 00:00:00

  • Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.

    abstract::To identify regulatory drivers of prostate cancer malignancy, we have assembled genome-wide regulatory networks (interactomes) for human and mouse prostate cancer from expression profiles of human tumors and of genetically engineered mouse models, respectively. Cross-species computational analysis of these interactome...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2014.03.017

    authors: Aytes A,Mitrofanova A,Lefebvre C,Alvarez MJ,Castillo-Martin M,Zheng T,Eastham JA,Gopalan A,Pienta KJ,Shen MM,Califano A,Abate-Shen C

    更新日期:2014-05-12 00:00:00

  • Does CSF1R Blockade Turn into Friendly Fire?

    abstract::In this issue of Cancer Cell, Kumar et al. describe how CSF1R blockade induces not only an expected deprivation of tumor-associated macrophages, but also an accumulation of tumor-infiltrating polymorphonuclear mononuclear cells caused by Cxcl-1 released from cancer-associated fibroblasts. ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2017.10.012

    authors: Greten TF

    更新日期:2017-11-13 00:00:00

  • Pathway-specific tumor suppression. Reduction of p27 accelerates gastrointestinal tumorigenesis in Apc mutant mice, but not in Smad3 mutant mice.

    abstract::Expression of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) is frequently reduced in human colorectal cancer, and this correlates with poor patient prognosis. To clarify the role of p27 in gastrointestinal (GI) cancer, we measured p27 expression, as well as the effect of germline deletion of p27, in 3 differen...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/s1535-6108(02)00054-5

    authors: Philipp-Staheli J,Kim KH,Payne SR,Gurley KE,Liggitt D,Longton G,Kemp CJ

    更新日期:2002-05-01 00:00:00

  • Metastatic colon cancer cells negotiate the intravasation Notch.

    abstract::In this issue of Cancer Cell, Sonoshita et al. report that Aes/Grg5 prevents metastasis of colorectal cancer cells by sequestering and inactivating Notch transcriptional effectors in distinct nuclear foci. Loss of Aes/Grg5 in invasive cancer cells where Notch is activated by stroma-expressed ligands promotes invasion,...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2011.01.003

    authors: Christofori G

    更新日期:2011-01-18 00:00:00

  • Is NF-kappaB2/p100 a direct activator of programmed cell death?

    abstract::Transcription factor NF-kappaB has been implicated in cancer development due to its ability to upregulate expression of genes with potentially prooncogenic functions, such as cell cycle regulators and antiapoptotic proteins (Karin et al., 2002). A recent report by suggests that a structural motif, a death domain (DD),...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/s1535-6108(02)00213-1

    authors: Häcker H,Karin M

    更新日期:2002-12-01 00:00:00

  • ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma.

    abstract::Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistanc...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2017.05.011

    authors: Marchesini M,Ogoti Y,Fiorini E,Aktas Samur A,Nezi L,D'Anca M,Storti P,Samur MK,Ganan-Gomez I,Fulciniti MT,Mistry N,Jiang S,Bao N,Marchica V,Neri A,Bueso-Ramos C,Wu CJ,Zhang L,Liang H,Peng X,Giuliani N,Draetta G

    更新日期:2017-07-10 00:00:00

  • The ups and downs of SRC regulation: tumor suppression by Cbp.

    abstract::Tight control of the tyrosine kinase activity of c-Src is critical for regulating its oncogenic potential. In a recent issue of Molecular Cell, Oneyama et al. (2008a) report that the membrane-bound adaptor protein Cbp (also known as PAG) can suppress c-Src-mediated cell transformation and tumorigenesis by binding and ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2008.05.011

    authors: Resh MD

    更新日期:2008-06-01 00:00:00

  • Twist1-induced invadopodia formation promotes tumor metastasis.

    abstract::The Twist1 transcription factor is known to promote tumor metastasis and induce Epithelial-Mesenchymal Transition (EMT). Here, we report that Twist1 is capable of promoting the formation of invadopodia, specialized membrane protrusions for extracellular matrix degradation. Twist1 induces PDGFRα expression, which in tu...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2011.01.036

    authors: Eckert MA,Lwin TM,Chang AT,Kim J,Danis E,Ohno-Machado L,Yang J

    更新日期:2011-03-08 00:00:00

  • ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis.

    abstract::Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase results in loss of bipolarity, detachment, and cell death of isolated endotheli...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2005.12.021

    authors: Mavria G,Vercoulen Y,Yeo M,Paterson H,Karasarides M,Marais R,Bird D,Marshall CJ

    更新日期:2006-01-01 00:00:00

  • Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells.

    abstract::Mutational activation of KRas is the first and most frequently detected genetic lesion in pancreatic ductal adenocarcinoma (PDAC). However, the precise role of oncogenic KRas in the pathogenesis of PDAC is not fully understood. Here, we report that the endogenous expression of oncogenic KRas suppresses premature senes...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2010.10.020

    authors: Lee KE,Bar-Sagi D

    更新日期:2010-11-16 00:00:00

  • PI3K regulatory subunits lose control in cancer.

    abstract::The PI3K signaling axis is frequently activated in cancer resulting from inactivation of its negative regulator PTEN or activating mutations of the p110alpha catalytic subunit of PI3K. In this issue of Cancer Cell, Jaiswal et al. report that mutations in the p85alpha regulatory subunit of PI3K can also activate this p...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2009.11.017

    authors: Berenjeno IM,Vanhaesebroeck B

    更新日期:2009-12-08 00:00:00

  • Vulnerabilities of mutant SWI/SNF complexes in cancer.

    abstract::Cancer genome sequencing efforts have revealed the novel theme that chromatin modifiers are frequently mutated across a wide spectrum of cancers. Mutations in genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are particularly prevalent, occurring in 20% of all human cancers. As these are typicall...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.ccr.2014.07.018

    authors: Helming KC,Wang X,Roberts CWM

    更新日期:2014-09-08 00:00:00

  • Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma.

    abstract::Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.05.020

    authors: Gomes AL,Teijeiro A,Burén S,Tummala KS,Yilmaz M,Waisman A,Theurillat JP,Perna C,Djouder N

    更新日期:2016-07-11 00:00:00

  • High-throughput Phenotyping of Lung Cancer Somatic Mutations.

    abstract::Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.06.022

    authors: Berger AH,Brooks AN,Wu X,Shrestha Y,Chouinard C,Piccioni F,Bagul M,Kamburov A,Imielinski M,Hogstrom L,Zhu C,Yang X,Pantel S,Sakai R,Watson J,Kaplan N,Campbell JD,Singh S,Root DE,Narayan R,Natoli T,Lahr DL,Tiro

    更新日期:2016-08-08 00:00:00

  • A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases.

    abstract::Transcriptional profiling of two isogenic models of transformation identifies a gene signature linking cancer with inflammatory and metabolic diseases. In accord with this common transcriptional program, many drugs used for treatment of diabetes and cardiovascular diseases inhibit transformation and tumor growth. Unex...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2010.01.022

    authors: Hirsch HA,Iliopoulos D,Joshi A,Zhang Y,Jaeger SA,Bulyk M,Tsichlis PN,Shirley Liu X,Struhl K

    更新日期:2010-04-13 00:00:00

  • TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer.

    abstract::The MAP3-kinase TGF-beta-activated kinase 1 (TAK1) critically modulates innate and adaptive immune responses and connects cytokine stimulation with activation of inflammatory signaling pathways. Here, we report that conditional ablation of TAK1 in liver parenchymal cells (hepatocytes and cholangiocytes) causes hepatoc...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2010.03.021

    authors: Bettermann K,Vucur M,Haybaeck J,Koppe C,Janssen J,Heymann F,Weber A,Weiskirchen R,Liedtke C,Gassler N,Müller M,de Vos R,Wolf MJ,Boege Y,Seleznik GM,Zeller N,Erny D,Fuchs T,Zoller S,Cairo S,Buendia MA,Prinz M,A

    更新日期:2010-05-18 00:00:00

  • Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas.

    abstract::Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading to a global reduction of the r...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2013.10.006

    authors: Bender S,Tang Y,Lindroth AM,Hovestadt V,Jones DT,Kool M,Zapatka M,Northcott PA,Sturm D,Wang W,Radlwimmer B,Højfeldt JW,Truffaux N,Castel D,Schubert S,Ryzhova M,Seker-Cin H,Gronych J,Johann PD,Stark S,Meyer J,Mil

    更新日期:2013-11-11 00:00:00

  • PDEF promotes luminal differentiation and acts as a survival factor for ER-positive breast cancer cells.

    abstract::Breast cancer is a heterogeneous disease and can be classified based on gene expression profiles that reflect distinct epithelial subtypes. We identify prostate-derived ETS factor (PDEF) as a mediator of mammary luminal epithelial lineage-specific gene expression and as a factor required for tumorigenesis in a subset ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2013.04.026

    authors: Buchwalter G,Hickey MM,Cromer A,Selfors LM,Gunawardane RN,Frishman J,Jeselsohn R,Lim E,Chi D,Fu X,Schiff R,Brown M,Brugge JS

    更新日期:2013-06-10 00:00:00

  • Settling a Nervous Stomach: The Neural Regulation of Enteric Cancer.

    abstract::The nervous system is emerging as a regulator of malignancy. In this issue of Cancer Cell, Hayakawa et al. demonstrate a feedforward signaling loop in which tumor-derived nerve growth factor promotes enteric tumor innervation, and recruited nerves drive cancer growth through acetylcholine-regulated Wnt signaling and s...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2016.12.008

    authors: Monje M

    更新日期:2017-01-09 00:00:00

  • CD103+ dendritic cells producing interleukin-12 in anticancer immunosurveillance.

    abstract::The mechanisms through which tumor antigen-specific T cells are elicited in natural or chemotherapy-induced immunosurveillance have been elusive. In this issue of Cancer Cell, two papers by Broz and colleagues and Ruffell and colleagues delineate an important role for a specific dendritic cell subset characterized by ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2014.10.008

    authors: Zitvogel L,Kroemer G

    更新日期:2014-11-10 00:00:00

  • In the pursuit of complexity: systems medicine in cancer biology.

    abstract::Adler et al., in a paper appearing in Nature Genetics, exploited the intersect of genetic information from expression profiles with that from array comparative genomic hybridization in human breast cancers to identify genes that may induce the transcription of the prognostic "wound response" expression signature. The ...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.ccr.2006.03.026

    authors: Liu ET,Kuznetsov VA,Miller LD

    更新日期:2006-04-01 00:00:00

  • Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer.

    abstract::Therapies that target estrogen signaling have transformed the treatment of breast cancer. However, the effectiveness of these agents is limited by the development of resistance. Here, an RNAi screen was used to identify modifiers of tamoxifen sensitivity. We demonstrate that CDK10 is an important determinant of resist...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2008.01.001

    authors: Iorns E,Turner NC,Elliott R,Syed N,Garrone O,Gasco M,Tutt AN,Crook T,Lord CJ,Ashworth A

    更新日期:2008-02-01 00:00:00

  • The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells.

    abstract::Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and a...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2012.03.014

    authors: Harris WJ,Huang X,Lynch JT,Spencer GJ,Hitchin JR,Li Y,Ciceri F,Blaser JG,Greystoke BF,Jordan AM,Miller CJ,Ogilvie DJ,Somervaille TC

    更新日期:2012-04-17 00:00:00

  • Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth.

    abstract::Neuropilin-1 (NRP1) guides the development of the nervous and vascular systems. Binding to either semaphorins or VEGF, NRP1 acts with plexins to regulate neuronal guidance, or with VEGFR2 to mediate vascular development. We have generated two monoclonal antibodies that bind to the Sema- and VEGF-binding domains of NRP...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2006.10.018

    authors: Pan Q,Chanthery Y,Liang WC,Stawicki S,Mak J,Rathore N,Tong RK,Kowalski J,Yee SF,Pacheco G,Ross S,Cheng Z,Le Couter J,Plowman G,Peale F,Koch AW,Wu Y,Bagri A,Tessier-Lavigne M,Watts RJ

    更新日期:2007-01-01 00:00:00

  • Same Script, Different Cast: Different Cell Origins Shape Molecular Features and Therapeutic Response in Glioblastoma.

    abstract::Glioblastoma is heterogeneous in the molecular subtypes based on transcriptomic classification. In this issue of Cancer Cell, Wang et al. define a cell-lineage-based stratification model for glioblastoma, highlighting how the cell of origin generates distinct molecular landscapes and therapeutic vulnerabilities from i...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2020.08.012

    authors: Wu S,Mischel PS

    更新日期:2020-09-14 00:00:00

  • EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis.

    abstract::The EZH2 histone methyltransferase mediates the humoral immune response and drives lymphomagenesis through formation of bivalent chromatin domains at critical germinal center (GC) B cell promoters. Herein we show that the actions of EZH2 in driving GC formation and lymphoma precursor lesions require site-specific bind...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.07.006

    authors: Béguelin W,Teater M,Gearhart MD,Calvo Fernández MT,Goldstein RL,Cárdenas MG,Hatzi K,Rosen M,Shen H,Corcoran CM,Hamline MY,Gascoyne RD,Levine RL,Abdel-Wahab O,Licht JD,Shaknovich R,Elemento O,Bardwell VJ,Melnick AM

    更新日期:2016-08-08 00:00:00

  • RalGDS is required for tumor formation in a model of skin carcinogenesis.

    abstract::To investigate the role of signaling by the small GTPase Ral, we have generated mice deficient for RalGDS, a guanine nucleotide exchange factor that activates Ral. We show that RalGDS is dispensable for mouse development but plays a substantial role in Ras-induced oncogenesis. Lack of RalGDS results in reduced tumor i...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2005.01.029

    authors: González-García A,Pritchard CA,Paterson HF,Mavria G,Stamp G,Marshall CJ

    更新日期:2005-03-01 00:00:00