Hallmarks of cancer: the next generation.


:The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.






Hanahan D,Weinberg RA




Has Abstract


2011-03-04 00:00:00
















  • A backup DNA repair pathway moves to the forefront.

    abstract::Chromosomal translocations between antigen receptor loci and oncogenes are a hallmark of lymphoid cancers. Several new studies now reveal that programmed DNA breaks created during assembly of antigen receptor genes can be channeled into an alternative DNA end-joining pathway that is implicated in the chromosomal trans...


    pub_type: 杂志文章


    authors: Nussenzweig A,Nussenzweig MC

    更新日期:2007-10-19 00:00:00

  • Parental imprinting of the mouse insulin-like growth factor II gene.

    abstract::We are studying mice that carry a targeted disruption of the gene encoding insulin-like growth factor II (IGF-II). Transmission of this mutation through the male germline results in heterozygous progeny that are growth deficient. In contrast, when the disrupted gene is transmitted maternally, the heterozygous offsprin...


    pub_type: 杂志文章


    authors: DeChiara TM,Robertson EJ,Efstratiadis A

    更新日期:1991-02-22 00:00:00

  • NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN.

    abstract::The tumor suppressor PTEN, a critical regulator for multiple cellular processes, is mutated or deleted frequently in various human cancers. Subtle reductions in PTEN expression levels have profound impacts on carcinogenesis. Here we show that PTEN level is regulated by ubiquitin-mediated proteasomal degradation, and p...


    pub_type: 杂志文章


    authors: Wang X,Trotman LC,Koppie T,Alimonti A,Chen Z,Gao Z,Wang J,Erdjument-Bromage H,Tempst P,Cordon-Cardo C,Pandolfi PP,Jiang X

    更新日期:2007-01-12 00:00:00

  • Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1.

    abstract::The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form...


    pub_type: 杂志文章


    authors: Bar-Peled L,Schweitzer LD,Zoncu R,Sabatini DM

    更新日期:2012-09-14 00:00:00

  • Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase.

    abstract::Dot1 is an evolutionarily conserved histone methyltransferase that methylates lysine-79 of histone H3 in the core domain. Unlike other histone methyltransferases, Dot1 does not contain a SET domain, and it specifically methylates nucleosomal histone H3. We have solved a 2.5 A resolution structure of the catalytic doma...


    pub_type: 杂志文章


    authors: Min J,Feng Q,Li Z,Zhang Y,Xu RM

    更新日期:2003-03-07 00:00:00

  • Formation of a rate-limiting intermediate in 5S RNA gene transcription.

    abstract::We have performed in vitro kinetic analyses of transcription from the 5S gene promoter in order to resolve the rate-limiting events which lead to accurate transcription of the 5S RNA gene. We demonstrate that a rate-limiting intermediate can be formed during an extended incubation prior to initiation of transcription....


    pub_type: 杂志文章


    authors: Bieker JJ,Martin PL,Roeder RG

    更新日期:1985-01-01 00:00:00

  • Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes.

    abstract::A major part of virulence for Plasmodium falciparum malaria infection, the most lethal parasitic disease of humans, results from increased rigidity and adhesiveness of infected host red cells. These changes are caused by parasite proteins exported to the erythrocyte using novel trafficking machinery assembled in the h...


    pub_type: 杂志文章


    authors: Maier AG,Rug M,O'Neill MT,Brown M,Chakravorty S,Szestak T,Chesson J,Wu Y,Hughes K,Coppel RL,Newbold C,Beeson JG,Craig A,Crabb BS,Cowman AF

    更新日期:2008-07-11 00:00:00

  • It takes a (dysfunctional) village to raise a tumor.

    abstract::The tumor microenvironment is known to play an important role in tumorigenesis. In this issue, Yang et al. (2008) demonstrate that mast cells heterozygous for the Nf1 gene promote the growth of neurofibromas in a mouse model of neurofibromatosis and that genetic and pharmacological inhibition of these cells is suffici...


    pub_type: 评论,杂志文章


    authors: Reilly KM,Van Dyke T

    更新日期:2008-10-31 00:00:00

  • Mammalian prion biology: one century of evolving concepts.

    abstract::Prions have been responsible for an entire century of tragic episodes. Fifty years ago, kuru decimated the population of Papua New Guinea. Then, iatrogenic transmission of prions caused more than 250 cases of Creutzfeldt-Jakob disease. More recently, transmission of bovine spongiform encephalopathy to humans caused a ...


    pub_type: 杂志文章,评审


    authors: Aguzzi A,Polymenidou M

    更新日期:2004-01-23 00:00:00

  • Alpha-amanitin-resistant D. melanogaster with an altered RNA polymerase II.

    abstract::Following EMS mutagenesis we recovered a mutant of D. melanogaster that grows at concentrations of alpha-amanitin lethal to wild-type. To our knowledge this mutant represents the first example of an amanitin-resistant eucaryotic organism. The amanitin resistance of the mutant (AmaC4) is due to an alteration in its DNA...


    pub_type: 杂志文章


    authors: Greenleaf AL,Borsett LM,Jiamachello PF,Coulter DE

    更新日期:1979-11-01 00:00:00

  • Processed Vg1 protein is an axial mesoderm inducer in Xenopus.

    abstract::Vg1 is a TGF beta-related growth factor encoded by a maternal mRNA localized to vegetal blastomeres in Xenopus embryos. Vg1 precursor protein is abundant in vegetal cells, but the processed mature form has not been readily detected and no activity has been demonstrated for the putative Vg1 mature protein. We have engi...


    pub_type: 杂志文章


    authors: Thomsen GH,Melton DA

    更新日期:1993-08-13 00:00:00

  • TGF-beta signaling specifies axons during brain development.

    abstract::In the mammalian brain, the specification of a single axon and multiple dendrites occurs early in the differentiation of most neuron types. Numerous intracellular signaling events for axon specification have been described in detail. However, the identity of the extracellular factor(s) that initiate neuronal polarity ...


    pub_type: 杂志文章


    authors: Yi JJ,Barnes AP,Hand R,Polleux F,Ehlers MD

    更新日期:2010-07-09 00:00:00

  • The 5' terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus.

    abstract::The 5' terminal structure of the mRNA synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus in the presence of S-adenosyl-L-methione consists of 7-methyl guanosine linked to 2'-O-methyl adenosine through a 5'-5' pyrophosphate bond as m7G(5')ppp(5')A-m-p ... The alpha and beta phosp...


    pub_type: 杂志文章


    authors: Abraham G,Rhodes DP,Banerjee AK

    更新日期:1975-05-01 00:00:00

  • A mechanism of formation of a persistent hybrid between elongating RNA and template DNA.

    abstract::At the replication origin of ColE1 plasmid, a persistent hybrid is formed between the primer precursor (RNA II) and its template DNA. The wild-type sequence in the region 13 to 20 bp upstream (-20 region) of the origin is required to form this persistent hybrid. While the template strand for transcription of this regi...


    pub_type: 杂志文章


    authors: Masukata H,Tomizawa J

    更新日期:1990-07-27 00:00:00

  • A ribonucleolytic rat torpedoes RNA polymerase II.

    abstract::Three recent papers reveal a fascinating link between pol II termination and ribonucleolytic decay of the nascent transcript by a 5'-3' exonuclease (yeast Rat1 and human Xrn2). The exonuclease travels with pol II and gains access to the nascent RNA after endonucleolytic cleavage at the poly(A) site or at a second cotr...


    pub_type: 杂志文章


    authors: Luo W,Bentley D

    更新日期:2004-12-29 00:00:00

  • Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis.

    abstract::Yeast mutants lacking meiotic proteins Zip1, Zip2, Zip3, Mer3, and/or Msh5 (ZMMs) were analyzed for recombination, synaptonemal complex (SC), and meiotic progression. At 33 degrees C, recombination-initiating double-strand breaks (DSBs) and noncrossover products (NCRs) form normally while formation of single-end invas...


    pub_type: 杂志文章


    authors: Börner GV,Kleckner N,Hunter N

    更新日期:2004-04-02 00:00:00

  • A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis.

    abstract::New neurons arise from quiescent adult neural progenitors throughout life in specific regions of the mammalian brain. Little is known about the embryonic origin and establishment of adult neural progenitors. Here, we show that Hopx+ precursors in the mouse dentate neuroepithelium at embryonic day 11.5 give rise to pro...


    pub_type: 杂志文章


    authors: Berg DA,Su Y,Jimenez-Cyrus D,Patel A,Huang N,Morizet D,Lee S,Shah R,Ringeling FR,Jain R,Epstein JA,Wu QF,Canzar S,Ming GL,Song H,Bond AM

    更新日期:2019-04-18 00:00:00

  • Protein degradation in E. coli: the lon mutation and bacteriophage lambda N and cII protein stability.

    abstract::The Ion gene of E. coli controls the stability of two bacteriophage lambda proteins. The functional half-life of the phage N gene product, measured by complementation, is increased about 5-fold in Ion mutant strains, from 2 min to 10 min. The chemical half-life of N protein, determined by its disappearance on polyacry...


    pub_type: 杂志文章


    authors: Gottesman S,Gottesman M,Shaw JE,Pearson ML

    更新日期:1981-04-01 00:00:00

  • Ubiquitylation of the 9-1-1 checkpoint clamp is independent of rad6-rad18 and DNA damage.

    abstract::A recent report proposed a function of the ubiquitin conjugation factors Rad6 and Rad18 comparable to the bacterial SOS response, controlling damage-induced transcriptional activation and contributing to checkpoint signaling. The relevant ubiquitylation target was identified as budding yeast Rad17, a subunit of the PC...


    pub_type: 杂志文章


    authors: Davies AA,Neiss A,Ulrich HD

    更新日期:2010-06-11 00:00:00

  • Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen.

    abstract::The large tumor antigen (LTag) of simian virus 40, an AAA(+) protein, is a hexameric helicase essential for viral DNA replication in eukaryotic cells. LTag functions as an efficient molecular machine powered by ATP binding and hydrolysis for origin DNA melting and replication fork unwinding. To understand how ATP bind...


    pub_type: 杂志文章


    authors: Gai D,Zhao R,Li D,Finkielstein CV,Chen XS

    更新日期:2004-10-01 00:00:00

  • Multilevel modulation of a sensory motor circuit during C. elegans sleep and arousal.

    abstract::Sleep is characterized by behavioral quiescence, homeostasis, increased arousal threshold, and rapid reversibility. Understanding how these properties are encoded by a neuronal circuit has been difficult, and no single molecular or neuronal pathway has been shown to be responsible for the regulation of sleep. Taking a...


    pub_type: 杂志文章


    authors: Cho JY,Sternberg PW

    更新日期:2014-01-16 00:00:00

  • Rethinking differentiation: stem cells, regeneration, and plasticity.

    abstract::Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it mea...


    pub_type: 杂志文章,评审


    authors: Sánchez Alvarado A,Yamanaka S

    更新日期:2014-03-27 00:00:00

  • Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3.

    abstract::Evasion of DNA damage-induced cell death, via mutation of the p53 tumor suppressor or overexpression of prosurvival Bcl-2 family proteins, is a key step toward malignant transformation and therapeutic resistance. We report that depletion or acute inhibition of checkpoint kinase 1 (Chk1) is sufficient to restore gamma-...


    pub_type: 杂志文章


    authors: Sidi S,Sanda T,Kennedy RD,Hagen AT,Jette CA,Hoffmans R,Pascual J,Imamura S,Kishi S,Amatruda JF,Kanki JP,Green DR,D'Andrea AA,Look AT

    更新日期:2008-05-30 00:00:00

  • The Implication of Early Chromatin Changes in X Chromosome Inactivation.

    abstract::During development, the precise relationships between transcription and chromatin modifications often remain unclear. We use the X chromosome inactivation (XCI) paradigm to explore the implication of chromatin changes in gene silencing. Using female mouse embryonic stem cells, we initiate XCI by inducing Xist and then...


    pub_type: 杂志文章


    authors: Żylicz JJ,Bousard A,Žumer K,Dossin F,Mohammad E,da Rocha ST,Schwalb B,Syx L,Dingli F,Loew D,Cramer P,Heard E

    更新日期:2019-01-10 00:00:00

  • Transcription gets to the checkpoint.

    abstract::The rapid cell proliferation characteristic of early animal embryos is accomplished with an abbreviated cell cycle and no DNA replication checkpoint. Blythe and Wieschaus provide evidence that nascent zygotic transcription precedes—and may trigger—this checkpoint at the midblastula transition. ...


    pub_type: 评论,杂志文章


    authors: Laver JD,Lipshitz HD

    更新日期:2015-03-12 00:00:00

  • STING Senses Microbial Viability to Orchestrate Stress-Mediated Autophagy of the Endoplasmic Reticulum.

    abstract::Constitutive cell-autonomous immunity in metazoans predates interferon-inducible immunity and comprises primordial innate defense. Phagocytes mobilize interferon-inducible responses upon engagement of well-characterized signaling pathways by pathogen-associated molecular patterns (PAMPs). The signals controlling deplo...


    pub_type: 杂志文章


    authors: Moretti J,Roy S,Bozec D,Martinez J,Chapman JR,Ueberheide B,Lamming DW,Chen ZJ,Horng T,Yeretssian G,Green DR,Blander JM

    更新日期:2017-11-02 00:00:00

  • Vesicular stomatitis virus glycoprotein is sorted and concentrated during export from the endoplasmic reticulum.

    abstract::Newly synthesized proteins are believed to move from the endoplasmic reticulum (ER) to the Golgi by bulk flow, and sorting is assumed to occur exclusively in the trans-Golgi network (TGN). Using quantitative immunoelectron microscopy, we demonstrate that vesicular stomatitis virus glycoprotein (VSV-G) is sorted from r...


    pub_type: 杂志文章


    authors: Balch WE,McCaffery JM,Plutner H,Farquhar MG

    更新日期:1994-03-11 00:00:00

  • Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration.

    abstract::Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated in neurodegenerative disease. Here, we find that a key consequence of ROS and neuronal mitochondrial dysfunction is the accumulation of lipid droplets (LD) in glia. In Drosophila, ROS triggers c-Jun-N-terminal Kinase (JNK) and Sterol Reg...


    pub_type: 杂志文章


    authors: Liu L,Zhang K,Sandoval H,Yamamoto S,Jaiswal M,Sanz E,Li Z,Hui J,Graham BH,Quintana A,Bellen HJ

    更新日期:2015-01-15 00:00:00

  • Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation.

    abstract::The transport kinetics of the influenza virus hemagglutinin from its site of synthesis to the apical plasma membrane of Madin-Darby canine kidney cells, a polarized epithelial cell line, were studied by a sensitive tryptic assay. Hemagglutinin acquired terminal sugars, as judged by sensitivity to endo-beta-N-acetylglu...


    pub_type: 杂志文章


    authors: Matlin KS,Simons K

    更新日期:1983-08-01 00:00:00

  • Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.

    abstract::Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autopha...


    pub_type: 杂志文章


    authors: Lee JH,Yu WH,Kumar A,Lee S,Mohan PS,Peterhoff CM,Wolfe DM,Martinez-Vicente M,Massey AC,Sovak G,Uchiyama Y,Westaway D,Cuervo AM,Nixon RA

    更新日期:2010-06-25 00:00:00