CHIPing away at cancer metastasis

Summaries of newsworthy papers include Neurotrophins to the rescue; Susceptibility to heart attack; Flies go large on RNAi; Zinc irritates an ion channel and The memory of things past

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 08 February 2009

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

This press release contains:

· Summaries of newsworthy papers:

Cell Biology: CHIPing away at cancer metastasis

Medicine: Neurotrophins to the rescue

Genetics: Susceptibility to heart attack

Nature: Flies go large on RNAi

Chemical Biology: Zinc irritates an ion channel

And finally…Neuroscience: The memory of things past

· 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.

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[1] Cell Biology: CHIPing away at cancer metastasis
DOI: 10.1038/ncb1839

Scientists have uncovered that an enzyme called CHIP suppresses breast cancer. The research, online in Nature Cell Biology, suggests that a target of the enzyme known as SRC-3 represents a promising new molecular target for this cancer.

Many solid tumours form metastases, where the cancer spreads from its site of origin – this is the main reason for therapeutic failure and cancer mortality. As such, there is a renewed focus on designing drugs that target molecular pathways required for metastasis.

Junn Yanagisawa and colleagues report that CHIP, which is known to degrade a number of cancer causing proteins, also acts to degrade the gene regulator SRC-3, which then suppresses tumour progression in breast cancer. In a mouse model, CHIP expression inhibited metastasis formation, while its deletion accelerated the process. Loss of CHIP leads to increased expression of a number of cancer associated proteins, causing cells to become invasive and to grow in an uncontrolled manner, both attributes of cancer cells.

Since SRC-3 accounts for the cancer suppressive role of CHIP, it presents a new therapeutic target for breast cancer.

Author contact:
Junn Yanagisawa (University of Tsukuba, Japan)
Tel: +81 29 853 6632; E-mail: [email protected]

[2] Medicine: Neurotrophins to the rescue
DOI: 10.1038/nm.1912

Scientists have identified a possible treatment in rodent and primate models linked to Alzheimer’s disease, according to a paper online this week in Nature Medicine.

BDNF – brain derived neurotrophic factor – is a protein thought to be important in long term memory. Previous studies have shown possible links between reduced levels of this protein in the brain and Alzheimer’s, which is characterized by accumulation of toxic proteins, neuron death, and cognitive dysfunction.

While no one animal model replicates all of these features, Mark Tuszynski and colleagues show that BDNF blocks neuron death in rat and primate brain lesion models, and cognitive dysfunction in aging rats and primates. In a genetic mouse model of Alzheimer’s disease, BDNF administration after disease onset restored cognitive function without affecting toxic protein accumulation.

These findings suggest that BDNF could be used to treat Alzheimer’s disease, or in combination with drugs that prevent toxic protein formation and aggregation.

Author contact:
Mark Tuszynski (University of California San Diego, La Jolla, CA, USA)
Tel: +1 858 534 8857; E-mail: [email protected]

[3], [4], [5], [6] & [7] Genetics: Susceptibility to heart attack

DOI: 10.1038/ng.307
DOI: 10.1038/ng.314
DOI: 10.1038/ng.323
DOI: 10.1038/ng.326
DOI: 10.1038/ng.327

Genetic variants that predispose to heart attack are reported in five studies published online this week in Nature Genetics. While the effects of these variants on risk of disease are small, further study should provide new biological insight into the mechanisms underlying coronary artery disease, particularly those involving inflammation and lipids.

Four of the studies present genome-wide association studies for heart attack. Jeanette Erdmann and colleagues identify a new susceptibility locus on chromosome 3, in a gene that is highly expressed in the cardiovascular system and may be involved in cell-cell adhesion.

David-Alexandre Trégouët and colleagues report an association with a cluster of variants spanning three genes on chromosome 6. One of these genes encodes apolipoprotein(a), the main protein component of lipoprotein(a), which is a known risk factor for coronary artery disease. The third report from Toshihiro Tanaka and colleagues shows that a variant in a gene called BRAP is associated with risk of myocardial infarction. BRAP binds to two other proteins that this group previously identified as risk factors, and which may be involved in inflammation.

The Myocardial Infarction Genetics Consortium reports three new risk loci and confirms six previously identified loci. Finally, in the fifth study by Daniel Gudbjartsson and colleagues, the authors carried out a genome-wide association for eosinophil numbers. Eosinophils are white blood cells involved in inflammatory processes. Five loci were identified, one of which was also associated with heart attack in six different populations.

Author contacts:
Jeanette Erdmann (University of Lübeck, Germany) Paper [3]
Tel: +49 451 5004857; E-mail: [email protected]

David-Alexandre Trégouët (INSERM, Paris, France) Paper [4]
Tel: +33 149779686; E-mail: [email protected]

Daniel Gudbjartsson (deCODE Genetics, Reykjavik, Iceland) Paper [5]
Tel: +354 5701964; E-mail: [email protected]

Additional media contact – paper [5]:
Edward Farmer (deCODE Genetics, New York, NY, USA)
Tel: +1 646 417 4555; E-mail: [email protected]

Toshihiro Tanaka (RIKEN, Yokohama, Japan) Paper [6]
Tel: +81 45503 9290; E-mail: [email protected]

Sekar Kathiresan (Massachusetts General Hospital, Boston, MA, USA) Paper [7]
Tel: +1 617 643 6120; E-mail: [email protected]

[8] Nature: Flies go large on RNAi
DOI: 10.1038/nature07712

Flies use a gene-silencing method called RNA interference (RNAi) to combat viral infection systemically, a Nature paper suggests.

To fight infection, multicellular organisms must be able to generate an immune response locally at the site of infection and further away at uninfected locations. It’s known that flies use RNAi to do the former, but the same process was thought to be unable to generate a systemic response. Not so, say Raul Andino and colleagues.

The team identified a key RNAi signalling pathway present in adult flies that is essential for antiviral RNAi immunity. Inoculating healthy flies with double-stranded RNA (dsRNA) — a core component of the RNAi machinery — generates an antiviral immune response even though no virus is present. It’s thought that the dsRNA spreads from cell to cell, generating a systemic antiviral immune response and that this systemic RNAi is a key component of the fly antiviral armoury.

Author contact:
Raul Andino (University of California, San Francisco, CA, USA)
Tel: +1 415 502 6358; E-mail: [email protected]

[9] Chemical Biology: Zinc irritates an ion channel
DOI: 10.1038/nchembio.146

Researchers have discovered how the body reacts to the negative effects of zinc over exposure. A paper online in Nature Chemical Biology, reports that a previously known sensor for other chemicals, also acts as a mediator for the sensory symptoms associated with zinc toxicity, such as pain.

Zinc is one of the most commonly used metals in industrial settings. While being essential for the function of hundreds of proteins, high concentrations are toxic to cells. Overexposure by inhalation can cause symptoms such as nausea, gastric pain and inflammation.

Ardem Patapoutian and colleagues found that zinc acts as a messenger that enters somatosensory neurons through minimally active TRPA1 channels. It then further activates the channel through an interaction with several intracellular residues. TRPA1 had been previously implicated as a sensor for several pungent phytochemicals, such as mustard oil, as well as extreme cold.

Author contact:
Ardem Patapoutian (The Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 9879; E-mail: [email protected]

[10] And finally…Neuroscience: The memory of things past
DOI: 10.1038/nn.2260

People can recognize a previously seen image, even when they have no conscious awareness of having seen it, finds a study online in Nature Neuroscience. Such recognition was thought to be associated with conscious, explicit memory, rather than unconscious, implicit memory. The study also finds that a specific pattern of electrical activity in the brain is associated with such unconscious recognition memory.

Joel Voss and Ken Paller showed people images, asking them to remember them, despite the distraction of a simultaneous numerical task. In a later test session, previously seen images were presented along with new similar images. Participants correctly recognized the previously seen image most of the time, although they were likely to report that they were guessing, not that they remembered the image itself. This suggests that the people can recognize an image, even without conscious awareness of it.

Recordings of electrical signals related to brain activity during the recognition test showed a distinct response when participants recognized an image without conscious awareness. These results suggest that implicit memory might contribute to recognition, which had been thought to require an explicit awareness of having previously seen something.

Author contact:
Joel Voss (Northwestern University, Evanston, IL, USA)
Tel: +1 847 204 9785; E-mail: [email protected]

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

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

[11] Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis
DOI: 10.1038/nature07713

[12] Dynamic expression of epidermal caspase 8 simulates a wound healing response
DOI: 10.1038/nature07687

[13] An unexpected twist in viral capsid maturation
DOI: 10.1038/nature07686

[14] Specific synapses develop preferentially among sister excitatory neurons in the neocortex
DOI: 10.1038/nature07722

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

[15] Requirement for Nudel and dynein for assembly of the lamin B spindle matrix
DOI: 10.1038/ncb1832

[16] Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis
DOI: 10.1038/ncb1833

[17] Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche
DOI: 10.1038/ncb1838

[18] Prions hijack tunnelling nanotubes for intercellular spread
DOI: 10.1038/ncb1841

[19] Nuclear transport factor directs localization of protein synthesis during mitosis
DOI: 10.1038/ncb1844

NATURE GEOSCIENCE (http://www.nature.com/ngeo)

[20] Preservation of iron(II) by carbon-rich matrices in a hydrothermal plume
DOI: 10.1038/ngeo433

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

[21] The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules
DOI: 10.1038/ni.1699

[22] Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-beta signaling pathway in Caenorhabditis elegans epidermis
DOI: 10.1038/ni.1700

[23] Cholesterol depletion associated with Leishmania major infection alters macrophage CD40 signalosome composition and effector function
DOI: 10.1038/ni.1705

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

[24] Ferroelectricity and polarity control in solid-state flip-flop supramolecular rotators
DOI: 10.1038/nmat2377

[25] Endohedral fullerenes for organic photovoltaic devices
DOI: 10.1038/nmat2379

[26] Towards wafer-size graphene layers by atmospheric pressure graphitization of silicon carbide
DOI: 10.1038/nmat2382

[27] Subnanometre platinum clusters as highly active and selective catalysts for the oxidative dehydrogenation of propane
DOI: 10.1038/nmat2384

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

[28] Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle
DOI: 10.1038/nm.1916

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

[29] Nanomole-scale Protein Solid-state NMR by Breaking Intrinsic 1H-T1 Boundaries
DOI: 10.1038/nmeth.1300

[30] Direct Determination of Haplotypes from Single DNA Molecules
DOI: 10.1038/nmeth.1301

[31] Quantitative interaction proteomics using mass spectrometry
DOI: 10.1038/nmeth.1302

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

[32] Mechanically interlocked calix[4]arene dimmers display reversible bond breakage under force
DOI:10.1038/nnano.2008.416

Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[33] Spike frequency adaptation mediates looming stimulus selectivity in a collision-detecting neuron
DOI: 10.1038/nn.2259

[34] Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill
DOI: 10.1038/nn.2261

[35] Slow glycinergic transmission mediated by transmitter pooling
DOI: 10.1038/nn.2265

[36] Different receptive fields in axons and dendrites underlie robust coding in motion-sensitive neurons
DOI: 10.1038/nn.2269

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

[37] Preparation of non-local superpositions of quasi-classical light states
DOI: 10.1038/nphys1199

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

[38] Transient ribosomal attenuation coordinates protein synthesis and co-translational folding
DOI: 10.1038/nsmb.1554

[39] Helix sliding in the stalk coiled coil of dynein couples ATPase and microtubule binding
DOI: 10.1038/nsmb.1555

[40] A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions
DOI: 10.1038/nsmb.1556

[41] Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
DOI: 10.1038/nsmb.1558

*************************************************************************************************************
GEOGRAPHICAL LISTING OF AUTHORS

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.

AUSTRALIA
Nedlands: 5
Perth: 5

AUSTRIA
Graz: 3

CANADA:
Hamilton: 7
Montreal: 7, 11

CHINA
Hong Kong: 5
Shanghai: 15

DENMARK
Copenhagen: 5

ESTONIA
Tallinn: 29

FINLAND
Helsinki: 3, 7

FRANCE
Lille: 4
Marseille: 22
Montpellier: 28
Orsay: 4
Palaiseau: 37
Paris: 3, 4, 7, 8, 16, 18
Strasbourg: 4
Toulouse: 4

GERMANY
Berlin: 26
Bozen: 5
Cologne: 5
Dortmund: 7
Erlangen: 25, 26
Freiburg: 5
Garching: 37
Heidelberg: 3
Kiel: 3, 4, 7
Lubeck: 3, 4, 7
Mainz: 3, 32
Mannheim: 3, 4
Martinsried: 36, 38
Munich: 3, 7, 36
Munster: 7
Neuherberg: 3, 4, 5, 7
Potsdam-Golm: 38
Regensburg: 3, 4, 7, 18
Stuttgart: 27

ICELAND
Reykjavik: 5, 7

INDIA
Kolkata: 23
Mumbai: 23
Pune: 23

ITALY
Bolzano: 5
Ferrara: 7
Genova: 41
Girona: 7
Milan: 3, 7
Naples: 18
Pavia: 3, 7
Parma 3, 7
Rome: 7
Rovigo: 7
Turin: 7
Verona: 5, 7

JAPAN
Ibaraki: 1
Kawaguchi: 24
Kitakyushu: 6
Osaka: 6, 11
Saitama: 1
Sapporo: 24
Sendai: 1
Tokyo: 6, 39
Tsukuba: 24
Yokohama: 6

NETHERLANDS
Groningen: 5, 19
Nijmegen: 8

NEW ZEALAND
Dunedin: 5

SOUTH KOREA
Puchon: 5
Seoul: 5

SPAIN
Barcelona: 3, 7, 16
Seville: 41

SWEDEN
Malmo: 3, 7
Uppsala: 5

SWITZERLAND
Zurich: 31

TAIWAN
Kaohsiung: 6

UNITED KINGDOM
Belfast: 4, 7
Cambridge: 3, 4, 7
Coventry: 29
Glasgow: 4
Leeds: 3, 4, 7, 39
Leicester: 3, 4, 7
London: 16, 41
Nottingham: 5

UNITED STATES OF AMERICA

California
Berkeley: 20, 26, 39
La Jolla: 2, 9, 12, 13, 15
Los Angeles: 2, 20
Pasadena: 13, 21
San Diego: 2, 9
San Francisco: 8, 30
Santa Barbara: 25

Colorado
Golden: 25

Connecticut
New Haven: 27

District of Columbia
Washington: 7, 25

Georgia
Atlanta: 5

Illinois
Argonne: 27
Chicago: 29
Evanston: 10
Urbana: 10

Maryland
Baltimore: 15
Bethesda: 3, 11, 17, 34

Massachusetts
Boston: 3, 7
Cambridge: 7
Framington: 7
Woods Hole: 20

Minnesota
St Paul: 20

Missouri
Kansas City: 7

Nebraska
Omaha: 15

New Mexico
Albuquerque: 26

New York
New York: 2, 14, 28
Stony Brook: 40

North Carolina
Durham: 5, 32, 34

Ohio
Cleveland: 29, 40
Columbus: 9

Oregon
Portland: 35

Pennsylvania
Philadelphia: 5, 7, 30
Pittsburgh: 13

Tennessee
Nashville: 7

Texas
Houston: 33

Virginia
Danville: 25

Washington
Seattle: 3, 7, 31

PRESS CONTACTS…

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

Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]

Katherine Anderson (Nature New York)
Tel: +1 212 726 9231; E-mail: [email protected]

Ruth Francis (Head of Press, 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)
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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 Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Alison Stoddart
Tel: +44 20 7843 4593; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)
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Tel: +1 212 726 9627; E-mail: [email protected]

Nature Nanotechnology (London)
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Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail: [email protected]

Nature Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: [email protected]

Nature Physics (London)
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Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)
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Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 08 Feb 2009

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