Oncology: Colon cancer stem cells

Summaries of newsworthy papers include Nanomaterials for imaging and therapy – Nature Materials, High times for memory – Nature Neuroscience, An unexpected mechanism of pain – Nature Neuroscience, Auditory repetition and dyslexia – Nature Neuroscience


For papers that will be published online on 19 November 2006

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Oncology: Colon cancer stem cells – Nature

Nanomaterials for imaging and therapy – Nature Materials

High times for memory – Nature Neuroscience

An unexpected mechanism of pain – Nature Neuroscience

Auditory repetition and dyslexia – Nature Neuroscience

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.

Warning: This document, and the Nature journal papers to which it refers, may contain information that is price sensitive (as legally defined, for example, in the UK Criminal Justice Act 1993 Part V) with respect to publicly quoted companies. Anyone dealing in securities using information contained in this document, or in advance copies of a Nature journal’s content, may be guilty of insider trading under the US Securities Exchange Act of 1934.

PICTURES: To obtain artwork from any of the journals, you must first obtain permission from the copyright holder (if named) or author of the research paper in question (if not).

NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: http://dx.doi.org/ (For example, http://dx.doi.org/10.1038/ng730). For more information about DOIs and Advance Online Publication, see http://www.nature.com/ng/aop/.



[1] & [2] Oncology: Colon cancer stem cells

DOI: 10.1038/nature05372

DOI: 10.1038/nature05384

A specific type of colon cancer cell capable of initiating tumour growth in mice is identified and characterized in a pair of related papers to be published online this week in Nature. Both papers lend support to the theory that, within a tumour, only a subset of cells — cancer stem cells — are responsible for tumour formation and maintenance.

John Dick and colleagues studied tumour growth by implanting human colon cancer cells under the kidney capsule of mice with a deficient immune system. They report that only a small population of these cells were able to initiate tumour growth and that these cells are found in the subset of colon cancer cells that express the cell surface protein CD133. This protein has previously been implicated as a marker for brain and prostate cancer stem cells. Ruggero De Maria and colleagues show that human colon cancer cells expressing CD133 also cause tumour growth when injected under the skin of immunodeficient mice.

These studies demonstrate that a small population of colon cancer cells, distinct from those that make up the bulk of a tumour, initiate tumour growth. The authors propose that the approaches used to identify and characterize these cells might aid future attempts to understand the processes involved in colon cancer and develop novel therapeutic strategies to treat the disease.

Author contact:

John Dick (University Health Network, Toronto, Canada)

Tel: + 1 416 581 7472; E-mail: [email protected]

Ruggero De Maria (Istituto Superiore di Sanità, Rome, Italy)
Tel: +39 06 4990 3121; E-mail: [email protected]

Other papers from Nature to be published online at the same time and with the same embargo:

[3] Variability and memory of protein levels in human cells

DOI: 10.1038/nature05316

[4] Clustered DNA motifs mark X chromosomes for repression by a dosage compensation complex

DOI: 10.1038/nature05338

[5] Robustness–epistasis link shapes the fitness landscape of a randomly drifting protein

DOI: 10.1038/nature05385

****************************** NATURE MATERIALS *************************** (http://www.nature.com/naturematerials)

[6] Nanomaterials for imaging and therapy

DOI: 10.1038/nmat1775

Imaging blood vessels using magnetic resonance and destroying malignant cells by near-infrared irradiation may both be possible in one integrated system, which is described in the December issue of Nature Materials.

The tiny system, produced by Hongjie Dai and colleagues, is a nanoparticle designed specifically with this dual function and with the additional advantage of being water soluble and non-toxic. It is made of an iron-cobalt alloy surrounded by a thin shell of graphitic carbon.

The iron-cobalt core has superior magnetic properties that provide high magnetic resonance imaging (MRI) contrast at lower doses than those required with conventional gadolinium contrast agents.

The graphitic shell has more than one purpose. It protects the iron-cobalt core, making it more stable and robust. Its surface can be functionalized so as to make the nanocrystal soluble in aqueous body fluids and allow a longer timespan to carry out imaging. Moreover, it absorbs near-infrared light. The authors argue that this phenomenon could be harnessed to generate localized heat and trigger a therapeutic effect, such as the destruction of cancer cells.

Author contact:

Hongjie Dai (Stanford University, Stanford, CA 94305, USA

Tel: +1 650 723 4518; E-mail: [email protected]

Other papers from Nature Materials to be published online at the same time and with the same embargo:

[7] The flexibility window in zeolites

DOI: 10.1038/nmat1784

*************************NATURE NEUROSCIENCE ************************


[8] High times for memory

DOI: 10.1038/nn1801

The active ingredient in marijuana – tetrahydrocannabinoid or THC – interferes with synchronized activity between neurons in the hippocampus of rats, according to a paper to be published in the December issue of Nature Neuroscience. The authors suggest that this may explain why the drug impairs memory.

György Buzsaki and colleagues recorded from multiple neurons in the hippocampus – a brain region known to be important for memory – of rats. Normally neurons in this region form groups that fire action potentials, or nerve impulses, together at about 4-10 times per second. But when the authors injected THC, or a related synthetic drug, into the hippocampus, this synchrony was disrupted. The drugs did not change the total number of action potentials produced, just their tendency to occur at the same time. Animals with less synchronized neural activity under the drug performed less well in a standard test of memory, suggesting that synchronized neural firing is important for normal hippocampal function.

Author contact:

György Buzsaki (Rutgers University, New Brunswick, NJ, USA)

Tel: +1 973 353 1080 x3131; E-mail: [email protected]

[9] An unexpected mechanism of pain

DOI: 10.1038/nn1804

A naturally produced pain reliever can exacerbate certain pain states rather than attenuate them in rodents, according to a paper in the December issue of Nature Neuroscience. The paper reports that an endogenous opioid – a small protein that activates the same receptors as opium or morphine – activates a different type of receptor to produce this effect.

Josephine Lai and colleagues studied dynorphin A, one of the endogenous opioids that normally act at opiate receptors to inhibit chronic pain. Elevated levels of dynorphin A are found in some chronic pain syndromes, such as that caused by nerve damage, but unlike other endogenous opioids, dynorphin A actually makes the pain worse. The authors now explain these puzzling results by showing that dynorphin A also activates bradykinin receptors in the spinal cord, which are known to cause hypersensitivity to pain. A drug that blocks bradykinin receptors protected against neuropathic pain, but only when dynorphin A was elevated. Mice lacking the bradykinin receptor also failed to show increased pain in response to dynorphin A.

These findings suggest that new opiate drugs should be evaluated in terms of their effects on bradykinin receptors – as well as opiate receptors – before being used to treat pain, and may prove useful in the development of novel approaches to drug development for chronic pain.

Author contact:

Josephine Lai (University of Arizona, Tucson, AZ, USA)

Tel: +1 520 626 2147; E-mail: [email protected]

[10] Auditory repetition and dyslexia

DOI: 10.1038/nn1800

Some dyslexic individuals have trouble encoding regularities in repeated sets of sounds, reports a study in the December issue of Nature Neuroscience.

Developmental dyslexia is a common condition characterized by difficulty in the acquisition of reading skills. The root cause of dyslexia remains controversial, but is believed to involve impairments in processing the sounds that make up language, which may be a necessary step in determining the meaning of words. Consistent with this hypothesis, dyslexics perform poorly compared to non-dyslexics on many auditory tasks.

Merav Ahissar and colleagues report that a subpopulation of dyslexics, those with learning disabilities, cannot use sound repetition to their advantage in auditory tasks. Dyslexic subjects performed as well as control subjects on two auditory discrimination tasks when sound stimuli were drawn from a large set. When the stimulus sets were small, the performance of the control subjects improved, presumably because they could use the regularities to help them perform the task. Dyslexic subjects, in contrast, failed to benefit from small stimulus sets involving sound repetitions, performing much worse than control subjects under those conditions. The authors suggest that this might be because dyslexics are unable to form a memory trace of the repeated stimuli. Whether this impairment generalizes to dyslexics who are not learning disabled, and whether it is causally related to reading difficulties, requires further investigation.

Author contact:

Merav Ahissar, (Hebrew University, Jerusalem, Israel)
Tel: +972 2588 3409; E-mail: [email protected]

Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:

[11] Simple fall-off pattern of correlated neural activity in the developing lateral geniculate nucleus

DOI: 10.1038/nn1799

[12] Propagating waves mediate information transfer in the motor cortex

DOI: 10.1038/nn1802

[13] The P2Y12 receptor regulates microglial activation by extracellular nucleotides

DOI: 10.1038/nn1805

[14] Hierarchical assembly of presynaptic components in defined C. elegans synapses

DOI: 10.1038/nn1806

[15] Cochlear efferent feedback balances interaural sensitivity

DOI: 10.1038/nn1807

[16] SYD-2/Liprin-alpha organizes presynaptic active zone formation through ELKS

DOI: 10.1038/nn1808

[17] fruitless regulates aggression and dominance in Drosophila

DOI: 10.1038/nn1809


Items from other Nature journals to be published online at the same time and with the same embargo:

NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)

[18] Forward chemical genetic approach identifies new role for GAPDH in insulin signaling

DOI: 10.1038/nchembio833

Nature PHYSICS (http://www.nature.com/naturephysics)

[19] Electrical detection of coherent 31P spin quantum states

DOI: 10.1038/nphys465

NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)

[20] Experimental realization of suspended atomic chains composed of different atomic species

DOI: 10.1038/nnano.2006.132

Nature MEDICINE (http://www.nature.com/naturemedicine)

[21] Microbial translocation is a cause of systemic immune activation in chronic HIV infection

DOI: 10.1038/nm1511

[22] Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells

DOI: 10.1038/nm1504

[23] Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation

DOI: 10.1038/nm1485

[24] Comprehensive volumetric optical microscopy in vivo

DOI: 10.1038/nm1450

Nature BIOTECHNOLOGY (http://www.nature.com/naturebiotechnolgy)

[25] The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT

DOI: 10.1038/nbt1256

[26] Blue fluorescent proteins with enhanced brightness and photostability from a structurally targeted library

DOI: 10.1038/nbt1264

NATURE GENETICS (http://www.nature.com/naturegenetics)

[27] Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion

DOI: 10.1038/ng1920

[28] Automating resequencing-based detection of insertion-deletion polymorphisms

DOI: 10.1038/ng1925

[29] In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication

DOI: 10.1038/ng1919

Nature IMMUNOLOGY (http://www.nature.com/natureimmunology)

[30] Hematopoietic progenitor kinase 1 negatively regulates T cell receptor signaling and T cell–mediated immune responses

DOI: 10.1038/ni1416

NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)

[31] Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells

DOI: 10.1038/ncb1513

[32] The armadillo protein p0071 regulates Rho signalling during cytokinesis

DOI: 10.1038/ncb1504

[33] Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies

DOI: 10.1038/ncb1499

[34] Regulation of cell shape by Cdc42 is mediated by the synergic actin-bundling activity of the Eps8–IRSp53 complex.

DOI: 10.1038/ncb1502

[35] A novel function of Drosophila eIF4A as a negative regulator of Dpp/BMP signalling mediating SMAD degradation

DOI: 10.1038/ncb1506

[36] Tyrosine phosphorylation controls PCNA function through protein stability

DOI: 10.1038/ncb1501

[37] Cyclin E–Cdk2 temporally regulates centrosome assembly and polarity establishment in C. elegans embryos

DOI: 10.1038/ncb1511

[38] Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination

DOI: 10.1038/ncb1510

Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)

[39] Crystal structure of RAC1 bound to its effector phospholipase C-beta2

DOI: 10.1038/nsmb1175

[40] Large movement of the C terminus of CLC-0 chloride channel during slow gating

DOI: 10.1038/nsmb1176

[41] Structure of the ribosome-bound cricket paralysis virus IRES RNA

DOI: 10.1038/nsmb1177

[42] Conformational restriction blocks glutamate receptor densensitization

DOI: 10.1038/nsmb1178

NATURE METHODS (http://www.nature.com/nmeth)

[43] Sensitive and specific method for detecting G protein–coupled receptor mRNAs

DOI: 10.1038/nmeth977


**The following article was published online on 10 November 2006 in Nature Structural and Molecular Biology but did not appear in last week’s press release. It is not under embargo but the rest of the papers on this release remain under embargo until Sunday 19 November 1800 London time / 1300 US Eastern time.**

[44] Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry

DOI: 10.1038/nsmb1179



The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Vienna: 17, 27


Campinas: 20

Juiz de Fora: 20


Leuven: 27


Ontario: 14

Toronto: 1


Chongqing: 23

Jinan: 44

Shanghai: 23


Bicetre: 21

Paris: 27

Strasbourg: 41
Berlin: 19, 41
Braunschweig: 34
Dresden: 37

Garching: 19

Halle: 32

Hamburg: 27, 34

Leipzig: 2

Ulm: 27

Jerusalem: 10
Rehovot: 3, 5

Tel Hashomer: 10


Catania: 2

Genoa: 22

Milan: 22, 34

Modena: 22

Palermo: 2

Rome: 2, 38

Venice: 22


Tokyo: 36


L’Hospitalet: 27


Taichung: 36


Utrecht: 29


London: 21


Birmingham: 27


Tempe: 7

Tuscon: 8, 9

Berkeley: 4

Davis: 40

La Jolla: 18

Los Angeles: 14

Pasadena: 26

San Francisco: 13, 21

Santa Barbara: 26

Santa Cruz: 16

Stanford: 6, 14

Chicago: 12, 21

Evanston: 10


Iowa City: 13

Baltimore: 25, 44

Bethesda: 21, 42, 43

Frederick: 31

Rockville: 43

Boston: 3, 15, 17, 24

Cambridge: 15, 24, 29

Minneapolis: 21

St Louis: 16, 33
New Jersey

Princeton: 44

Rochester: 11, 35
New York

New York: 13, 14, 18
North Carolina

Chapel Hill: 39

Cleveland: 21


Portland: 21

Kennett Square: 31

Philadelphia: 21


Memphis: 33

Houston: 30, 36, 41, 42

San Antonio: 12


Salt Lake City: 13, 19

Seattle: 27, 28


For media inquiries relating to embargo policy for all the Nature Research Journals:

Katherine Anderson (Nature London)

Tel: +44 20 7843 4502; E-mail: [email protected]

Ruth Francis (Senior Press Officer, Nature, London)

Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Biotechnology (New York)

Peter Hare

Tel: +1 212 726 9284; E-mail: [email protected]

Nature Cell Biology (London)

Bernd Pulverer

Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)

Andrea Garvey

Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)

Orli Bahcall

Tel: +1 212 726 9311; E-mail: [email protected]

Nature Immunology (New York)

Laurie Dempsey

Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)

Maria Bellantone

Tel: +44 20 7843 4556; E-mail: [email protected]

Nature Medicine (New York)

Juan Carlos Lopez

Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)

Allison Doerr

Tel: +1 212 726 9393; E-mail: [email protected]

Nature Nanotechnology (London)

Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)

Sandra Aamodt (based in California)

Tel: +1 530 795 3256; E-mail: [email protected]

Nature Physics (London)

Alison Wright

Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)

Michelle Montoya

Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 19 Nov 2006

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