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

authors： Resh MD

更新日期：2008-06-01 00:00:00

abstract：:The protein kinase PKB/Akt has long been associated with regulating signaling pathways that promote cell survival and cell growth, for example, in response to growth factors. In contrast, the DNA-dependent protein kinase (DNA-PK) is required for the repair of DNA damage and for cell survival after exposure to DNA-dama...

journal_title：Cancer cell

authors： Lees-Miller SP

更新日期：2008-05-01 00:00:00

abstract：:Abnormal activation of the epidermal growth factor receptor (EGFR) and its homolog HER2 (Neu/ErbB2) has been associated with many human cancers, and monoclonal antibodies targeting EGFR and HER2 are effective anticancer therapies. Structural studies of these receptors and antibodies have revealed much about how they f...

journal_title：Cancer cell

authors： Leahy DJ

更新日期：2008-04-01 00:00:00

abstract：:Small numbers of proangiogenic bone marrow-derived cells (BMDCs) can play pivotal roles in tumor progression. In this issue of Cancer Cell, two papers, utilizing different tumor angiogenesis models, both find that activated MMP-9 delivered by BMDCs modulates neovessel remodeling, thereby promoting tumor growth. The ch...

journal_title：Cancer cell

authors： Seandel M,Butler J,Lyden D,Rafii S

更新日期：2008-03-01 00:00:00

abstract：:Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in human malignancies. Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel wi...

journal_title：Cancer cell

authors： Petrocca F,Visone R,Onelli MR,Shah MH,Nicoloso MS,de Martino I,Iliopoulos D,Pilozzi E,Liu CG,Negrini M,Cavazzini L,Volinia S,Alder H,Ruco LP,Baldassarre G,Croce CM,Vecchione A

更新日期：2008-03-01 00:00:00

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

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

abstract：:It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single premalignant HER-2...

journal_title：Cancer cell

authors： Hüsemann Y,Geigl JB,Schubert F,Musiani P,Meyer M,Burghart E,Forni G,Eils R,Fehm T,Riethmüller G,Klein CA

更新日期：2008-01-01 00:00:00

abstract：:A key characteristic of stem cells and cancer cells is their ability to self-renew. To test if Wnt signaling can regulate the self-renewal of both stem cells and cancer cells in the hematopoietic system, we developed mice that lack beta-catenin in their hematopoietic cells. Here we show that beta-catenin-deficient mic...

journal_title：Cancer cell

authors： Zhao C,Blum J,Chen A,Kwon HY,Jung SH,Cook JM,Lagoo A,Reya T

更新日期：2007-12-01 00:00:00

abstract：:Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) initiated by expression of the p210-BCR-ABL fusion protein. We demonstrate in a murine model of p210-BCR-ABL-induced MPD that gene targeting of Rac1 and Rac2 significantly delays or abrogates disease development. Attenuation of the disease...

journal_title：Cancer cell

authors： Thomas EK,Cancelas JA,Chae HD,Cox AD,Keller PJ,Perrotti D,Neviani P,Druker BJ,Setchell KD,Zheng Y,Harris CE,Williams DA

更新日期：2007-11-01 00:00:00

abstract：:It is believed that Mdm2 suppresses p53 in two ways: transcriptional inhibition by direct binding, and degradation via its E3 ligase activity. To study these functions physiologically, we generated mice bearing a single-residue substitution (C462A) abolishing the E3 function without affecting p53 binding. Unexpectedly...

journal_title：Cancer cell

authors： Itahana K,Mao H,Jin A,Itahana Y,Clegg HV,Lindström MS,Bhat KP,Godfrey VL,Evan GI,Zhang Y

更新日期：2007-10-01 00:00:00

abstract：:The BCL6 gene is a key factor necessary for formation of germinal centers and is implicated in pathogenesis of diffuse large B cell lymphoma (DLBCL). In this issue of Cancer Cell, Saito and colleagues explore regulation of BCL6 gene expression by CD40-NF-kappaB signaling pathway and show that the IRF4 transcriptional ...

journal_title：Cancer cell

authors： Lossos IS

更新日期：2007-09-01 00:00:00

abstract：:The cell culture environment (substrate, atmosphere, and medium) can have a significant influence on the characteristics of cells that propagate from clinical samples. In this issue of Cancer Cell, Ince and colleagues report improved conditions for the culture of primary human breast epithelial cells. They demonstrate...

journal_title：Cancer cell

authors： Shay JW,Wright WE

更新日期：2007-08-01 00:00:00

abstract：:Acute promyelocytic leukemia (APL) is caused by chromosomal translocations that involve the retinoic acid receptor alpha (RAR) and several other genes to yield X-RAR fusion proteins. Unlike wild-type RARs, which require heterodimerization with the retinoid X receptor (RXR) for their function as DNA-binding transcripti...

journal_title：Cancer cell

authors： Minucci S,Pelicci PG

更新日期：2007-07-01 00:00:00

abstract：:Angiogenesis is a hallmark of solid tumors, and disruption of tumor vasculature is an active anticancer therapy in some cases. Several proteins expressed on the surface of tumor endothelium have been identified during the last decade. However, due to the expression in both physiological and tumor angiogenesis, only a ...

journal_title：Cancer cell

authors： Li JL,Harris AL

更新日期：2007-06-01 00:00:00

abstract：:PPARgamma is a member of the nuclear receptor family for which agonist ligands have antigrowth effects. However, clinical studies using PPARgamma ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPARgamma activation with chemotherapeutic agents in current use for specifi...

journal_title：Cancer cell

authors： Girnun GD,Naseri E,Vafai SB,Qu L,Szwaya JD,Bronson R,Alberta JA,Spiegelman BM

更新日期：2007-05-01 00:00:00

abstract：:HIF-2alpha promotes von Hippel-Lindau (VHL)-deficient renal clear cell carcinoma (RCC) tumorigenesis, while HIF-1alpha inhibits RCC growth. As HIF-1alpha antagonizes c-Myc function, we hypothesized that HIF-2alpha might enhance c-Myc activity. We demonstrate here that HIF-2alpha promotes cell-cycle progression in hypo...

journal_title：Cancer cell

authors： Gordan JD,Bertout JA,Hu CJ,Diehl JA,Simon MC

更新日期：2007-04-01 00:00:00

abstract：:Mutations in the EGFR kinase are a cause of non-small-cell lung cancer. To understand their mechanism of activation and effects on drug binding, we studied the kinetics of the L858R and G719S mutants and determined their crystal structures with inhibitors including gefitinib, AEE788, and a staurosporine. We find that ...

journal_title：Cancer cell

authors： Yun CH,Boggon TJ,Li Y,Woo MS,Greulich H,Meyerson M,Eck MJ

更新日期：2007-03-01 00:00:00

abstract：:It is established that p38 MAPK can negatively regulate tumorigenesis, but the mechanism is incompletely understood. A new study in this issue of Cancer Cell shows that p38 MAP kinase plays a selective role in tumor initiation mediated by oxidative stress. ...

journal_title：Cancer cell

authors： Kennedy NJ,Cellurale C,Davis RJ

更新日期：2007-02-01 00:00:00

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

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

abstract：:There is currently much interest in the idea of restoring p53 activity in tumor cells by inhibiting Hdm2/Mdm2. However, it has remained unclear whether this would also activate p53 in normal cells. Using a switchable endogenous p53 mouse model, which allows rapid and reversible toggling of p53 status between wild-type...

journal_title：Cancer cell

authors： Ringshausen I,O'Shea CC,Finch AJ,Swigart LB,Evan GI

更新日期：2006-12-01 00:00:00

abstract：:BCL-2 proteins are critical for cell survival and are overexpressed in many tumors. ABT-737 is a small-molecule BH3 mimetic that exhibits single-agent activity against lymphoma and small-cell lung cancer in preclinical studies. We here report that ABT-737 effectively kills acute myeloid leukemia blast, progenitor, and...

journal_title：Cancer cell

authors： Konopleva M,Contractor R,Tsao T,Samudio I,Ruvolo PP,Kitada S,Deng X,Zhai D,Shi YX,Sneed T,Verhaegen M,Soengas M,Ruvolo VR,McQueen T,Schober WD,Watt JC,Jiffar T,Ling X,Marini FC,Harris D,Dietrich M,Estrov Z,McC

更新日期：2006-11-01 00:00:00

abstract：:The genetic mechanisms responsible for increased incidence of lymphoma in immunocompromised individuals have not been fully elucidated. We show that, in a line of TCR transgenic TG-B mice, an insertional mutation in one allele of the Epm2a locus and epigenetic silencing of another led to a high rate of lymphoma with e...

journal_title：Cancer cell

authors： Wang Y,Liu Y,Wu C,Zhang H,Zheng X,Zheng Z,Geiger TL,Nuovo GJ,Liu Y,Zheng P

更新日期：2006-09-01 00:00:00

abstract：:Overexpression of Bcl-xL, loss of p19 ARF, and loss of p53 all accelerate Myc oncogenesis. All three lesions are implicated in suppressing Myc-induced apoptosis, suggesting that this is a common mechanism by which they synergize with Myc. However, using an acutely switchable model of Myc-induced tumorigenesis, we demo...

journal_title：Cancer cell

authors： Finch A,Prescott J,Shchors K,Hunt A,Soucek L,Dansen TB,Swigart LB,Evan GI

更新日期：2006-08-01 00:00:00

abstract：:A fundamental property of cancer cells is the preferential utilization of glycolysis over aerobic respiration to produce ATP. Renewed interest in understanding the mechanism underlying this metabolic shift in energy production is broadening our understanding of the relationship between cancer and cellular metabolism. ...

journal_title：Cancer cell

authors： Assaily W,Benchimol S

更新日期：2006-07-01 00:00:00

abstract：:Even in the presence of an adequate oxygen supply, many tumors metabolize the majority of the glucose they take up through glycolysis. It has been a long-held belief that this glycolytic phenotype is due to cancer-specific defects in mitochondrial oxidative phosphorylation. In this issue of Cancer Cell, Fantin et al. ...

journal_title：Cancer cell

authors： Bui T,Thompson CB

更新日期：2006-06-01 00:00:00

abstract：:Our understanding of Ewing's sarcoma development mediated by the EWS/FLI fusion protein has been limited by a lack of knowledge regarding the tumor cell of origin. To circumvent this, we analyzed the function of EWS/FLI in Ewing's sarcoma itself. By combining retroviral-mediated RNA interference with reexpression stud...

journal_title：Cancer cell

authors： Smith R,Owen LA,Trem DJ,Wong JS,Whangbo JS,Golub TR,Lessnick SL

更新日期：2006-05-01 00:00:00

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

authors： Liu ET,Kuznetsov VA,Miller LD

更新日期：2006-04-01 00:00:00

abstract：:Rapamycin analogs that inhibit mTOR signaling have antitumor activity against certain lymphomas, but treatment of solid tumors has been less encouraging despite inhibition of mTOR function. Two recent papers give insight into the potential use of mTOR inhibitors. O'Reilly et al. provide evidence that poor tumor respon...

journal_title：Cancer cell

authors： Easton JB,Kurmasheva RT,Houghton PJ

更新日期：2006-03-01 00:00:00

abstract：:We used small molecule screening to discover compounds and mechanisms for overcoming E6 oncogene-mediated drug resistance. Using high-throughput screening in isogenic cell lines, we identified compounds that potentiate doxorubicin's lethality in E6-expressing colon cancer cells. Such compounds included quaternary ammo...

journal_title：Cancer cell

authors： Smukste I,Bhalala O,Persico M,Stockwell BR

更新日期：2006-02-01 00:00:00

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

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

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...

journal_title：Cancer cell

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

更新日期：2005-12-01 00:00:00

abstract：:Epigenetic changes are the most common alterations in human cancer, but it has been difficult to sort out cause and effect from studies of human tumors. Several recent nonlethal mouse models implicate both hypomethylation and loss of imprinting (LOI) in tumor formation, including a paper in this issue of Cancer Cell s...

journal_title：Cancer cell

authors： Feinberg AP

更新日期：2005-10-01 00:00:00

abstract：:Mechanisms for breast cancer recurrence and metastases are poorly understood. New evidence from a transgenic mouse mammary tumor model suggests that the transcriptional repressor, Snail, may play a role in recurrence by downregulating E-cadherin and inducing an epithelial-to-mesenchymal transition. Preliminary informa...

journal_title：Cancer cell

authors： Davidson NE,Sukumar S

更新日期：2005-09-01 00:00:00

abstract：:Mutations in VHL, RET, NF1, SDHB, SDHC, and SDHD can give rise to pheochromocytoma/paraganglioma. These different genetic lesions may all act by decreasing the activity of a 2-oxoglutarate-dependent oxygenase, SM-20/EglN3/PHD3, resulting in reduced apoptosis of neural crest cells during development. ...

journal_title：Cancer cell

authors： Maxwell PH

更新日期：2005-08-01 00:00:00

abstract：:Gankyrin is an ankyrin repeat oncoprotein commonly overexpressed in hepatocellular carcinomas. Gankyrin interacts with the S6 proteasomal ATPase and accelerates the degradation of the tumor suppressor Rb. We show here that gankyrin has an antiapoptotic activity in cells exposed to DNA damaging agents. Downregulation o...

journal_title：Cancer cell

authors： Higashitsuji H,Higashitsuji H,Itoh K,Sakurai T,Nagao T,Sumitomo Y,Masuda T,Dawson S,Shimada Y,Mayer RJ,Fujita J

更新日期：2005-07-01 00:00:00

abstract：:Cancer therapeutics are primarily thought to work by inducing apoptosis in tumor cells. However, various tumor suppressors and oncogenes have been shown to regulate senescence in normal cells, and senescence bypass appears to be an important step in the development of cancer. Cellular senescence limits the replicative...

journal_title：Cancer cell

authors： Dimri GP

更新日期：2005-06-01 00:00:00

abstract：:A human pancreatic cancer progression model from intraepithelial neoplasia to ductal adenocarcinoma has been proposed. This process has been modeled in the mouse by activation of mutant Kras in pancreatic progenitor cells. In this issue of Cancer Cell, present a modification of their initial model by introducing a mut...

journal_title：Cancer cell

authors： Siveke JT,Schmid RM

更新日期：2005-05-01 00:00:00

abstract：:Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crysta...

journal_title：Cancer cell

authors： Li S,Schmitz KR,Jeffrey PD,Wiltzius JJ,Kussie P,Ferguson KM

更新日期：2005-04-01 00:00:00

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

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

更新日期：2005-03-01 00:00:00

abstract：:The SH2-containing tyrosine phosphatase Shp2 (PTPN11) is required for growth factor and cytokine signaling. Germline Shp2 mutations cause Noonan Syndrome (NS), which is associated with increased risk of juvenile myelomonocytic leukemia (JMML). Somatic Shp2 mutations occur in sporadic JMML and other leukemias. We found...

journal_title：Cancer cell

authors： Mohi MG,Williams IR,Dearolf CR,Chan G,Kutok JL,Cohen S,Morgan K,Boulton C,Shigematsu H,Keilhack H,Akashi K,Gilliland DG,Neel BG

更新日期：2005-02-01 00:00:00