Tissue curvature and apicobasal mechanical tension imbalance instruct cancer morphogenesis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02

AUTHORS

Hendrik A. Messal, Silvanus Alt, Rute M. M. Ferreira, Christopher Gribben, Victoria Min-Yi Wang, Corina G. Cotoi, Guillaume Salbreux, Axel Behrens

ABSTRACT

Tubular epithelia are a basic building block of organs and a common site of cancer occurrence1-4. During tumorigenesis, transformed cells overproliferate and epithelial architecture is disrupted. However, the biophysical parameters that underlie the adoption of abnormal tumour tissue shapes are unknown. Here we show in the pancreas of mice that the morphology of epithelial tumours is determined by the interplay of cytoskeletal changes in transformed cells and the existing tubular geometry. To analyse the morphological changes in tissue architecture during the initiation of cancer, we developed a three-dimensional whole-organ imaging technique that enables tissue analysis at single-cell resolution. Oncogenic transformation of pancreatic ducts led to two types of neoplastic growth: exophytic lesions that expanded outwards from the duct and endophytic lesions that grew inwards to the ductal lumen. Myosin activity was higher apically than basally in wild-type cells, but upon transformation this gradient was lost in both lesion types. Three-dimensional vertex model simulations and a continuum theory of epithelial mechanics, which incorporate the cytoskeletal changes observed in transformed cells, indicated that the diameter of the source epithelium instructs the morphology of growing tumours. Three-dimensional imaging revealed that-consistent with theory predictions-small pancreatic ducts produced exophytic growth, whereas large ducts deformed endophytically. Similar patterns of lesion growth were observed in tubular epithelia of the liver and lung; this finding identifies tension imbalance and tissue curvature as fundamental determinants of epithelial tumorigenesis. More... »

PAGES

126-130

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41586-019-0891-2

DOI

http://dx.doi.org/10.1038/s41586-019-0891-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111779575

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30700911


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "The Francis Crick Institute", 
          "id": "https://www.grid.ac/institutes/grid.451388.3", 
          "name": [
            "Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Messal", 
        "givenName": "Hendrik A.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Max Delbr\u00fcck Center for Molecular Medicine", 
          "id": "https://www.grid.ac/institutes/grid.419491.0", 
          "name": [
            "Theoretical Physics of Biology Laboratory, The Francis Crick Institute, London, UK", 
            "Max Delbru\u0308ck Center for Molecular Medicine, Berlin, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Alt", 
        "givenName": "Silvanus", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University College London", 
          "id": "https://www.grid.ac/institutes/grid.83440.3b", 
          "name": [
            "Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK", 
            "Cell Death, Cancer and Inflammation Laboratory, University College London Cancer Institute, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ferreira", 
        "givenName": "Rute M. M.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The Francis Crick Institute", 
          "id": "https://www.grid.ac/institutes/grid.451388.3", 
          "name": [
            "Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gribben", 
        "givenName": "Christopher", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The Francis Crick Institute", 
          "id": "https://www.grid.ac/institutes/grid.451388.3", 
          "name": [
            "Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Victoria Min-Yi", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Royal Free Hospital", 
          "id": "https://www.grid.ac/institutes/grid.426108.9", 
          "name": [
            "Institute of Liver Studies, King\u2019s College Hospital, London, UK", 
            "Department of Cellular Pathology, The Royal Free Hospital, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cotoi", 
        "givenName": "Corina G.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The Francis Crick Institute", 
          "id": "https://www.grid.ac/institutes/grid.451388.3", 
          "name": [
            "Theoretical Physics of Biology Laboratory, The Francis Crick Institute, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Salbreux", 
        "givenName": "Guillaume", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "King's College London", 
          "id": "https://www.grid.ac/institutes/grid.13097.3c", 
          "name": [
            "Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK", 
            "Faculty of Life Sciences and Medicine, King\u2019s College London, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Behrens", 
        "givenName": "Axel", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.15252/embr.201439246", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002160543"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nphys3224", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002387502", 
          "https://doi.org/10.1038/nphys3224"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccr.2012.02.022", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002516265"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cub.2015.12.063", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002758530"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb3092", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004570820", 
          "https://doi.org/10.1038/ncb3092"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2014.06.019", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007013021"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.943001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007211161"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1083/jcb.146.1.149", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011427771"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1535-6108(03)00309-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012489329"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccell.2016.09.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017556468"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci29988", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019516471"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci29988", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019516471"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1083/jcb.130.3.613", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019982175"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/dev.090159", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021220233"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-13-1911", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021894849"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nn.2467", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022194277", 
          "https://doi.org/10.1038/nn.2467"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nn.2467", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022194277", 
          "https://doi.org/10.1038/nn.2467"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scisignal.aaa8859", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022665209"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajpendo.00321.2002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022745317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2014.12.021", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024162945"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/dvg.20397", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025936015"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/cvr/cvq144", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027797834"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/cvr/cvq144", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027797834"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.devcel.2009.11.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028326990"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb3246", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028738506", 
          "https://doi.org/10.1038/ncb3246"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cub.2014.03.059", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031757440"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.gastro.2011.04.043", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032119464"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2011.11.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032774444"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1083/jcb.201202108", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034402475"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccr.2005.08.010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038845984"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccr.2005.08.010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038845984"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci57131", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041825328"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-213x-1-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042905963", 
          "https://doi.org/10.1186/1471-213x-1-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2010.09.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043020547"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/emboj.2013.204", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046241891"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.249409.114", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048897105"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.neo.2016.08.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048945830"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/onc.2015.441", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049305989", 
          "https://doi.org/10.1038/onc.2015.441"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nn.2644", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051495272", 
          "https://doi.org/10.1038/nn.2644"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1088/2057-1739/2/3/035004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059183609"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1103/revmodphys.85.1143", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060839747"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1103/revmodphys.85.1143", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060839747"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074630051", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.20162024", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083862081"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1098/rstb.2015.0520", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084197262"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1103/physreve.96.032404", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091497624"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1103/physreve.96.032404", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091497624"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.celrep.2017.09.093", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092348715"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/dev.151282", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1093048940"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-02", 
    "datePublishedReg": "2019-02-01", 
    "description": "Tubular epithelia are a basic building block of organs and a common site of cancer occurrence1-4. During tumorigenesis, transformed cells overproliferate and epithelial architecture is disrupted. However, the biophysical parameters that underlie the adoption of abnormal tumour tissue shapes are unknown. Here we show in the pancreas of mice that the morphology of epithelial tumours is determined by the interplay of cytoskeletal changes in transformed cells and the existing tubular geometry. To analyse the morphological changes in tissue architecture during the initiation of cancer, we developed a three-dimensional whole-organ imaging technique that enables tissue analysis at single-cell resolution. Oncogenic transformation of pancreatic ducts led to two types of neoplastic growth: exophytic lesions that expanded outwards from the duct and endophytic lesions that grew inwards to the ductal lumen. Myosin activity was higher apically than basally in wild-type cells, but upon transformation this gradient was lost in both lesion types. Three-dimensional vertex model simulations and a continuum theory of epithelial mechanics, which incorporate the cytoskeletal changes observed in transformed cells, indicated that the diameter of the source epithelium instructs the morphology of growing tumours. Three-dimensional imaging revealed that-consistent with theory predictions-small pancreatic ducts produced exophytic growth, whereas large ducts deformed endophytically. Similar patterns of lesion growth were observed in tubular epithelia of the liver and lung; this finding identifies tension imbalance and\u00a0tissue curvature as fundamental determinants of epithelial tumorigenesis.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41586-019-0891-2", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0090-0028", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7742", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "566"
      }
    ], 
    "name": "Tissue curvature and apicobasal mechanical tension imbalance instruct cancer morphogenesis", 
    "pagination": "126-130", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "e1dd841c5587168946ca8b1ceafc84db35b80e4276f79fde2efda71d9f0cded9"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30700911"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0410462"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41586-019-0891-2"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1111779575"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41586-019-0891-2", 
      "https://app.dimensions.ai/details/publication/pub.1111779575"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:57", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000365_0000000365/records_71677_00000002.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41586-019-0891-2"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41586-019-0891-2'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41586-019-0891-2'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41586-019-0891-2'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41586-019-0891-2'


 

This table displays all metadata directly associated to this object as RDF triples.

262 TRIPLES      21 PREDICATES      72 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41586-019-0891-2 schema:about anzsrc-for:11
2 anzsrc-for:1112
3 schema:author N2fd02592d54e498cbfa4dadc0a1b4010
4 schema:citation sg:pub.10.1038/ncb3092
5 sg:pub.10.1038/ncb3246
6 sg:pub.10.1038/nn.2467
7 sg:pub.10.1038/nn.2644
8 sg:pub.10.1038/nphys3224
9 sg:pub.10.1038/onc.2015.441
10 sg:pub.10.1186/1471-213x-1-4
11 https://app.dimensions.ai/details/publication/pub.1074630051
12 https://doi.org/10.1002/dvg.20397
13 https://doi.org/10.1016/j.ccell.2016.09.001
14 https://doi.org/10.1016/j.ccr.2005.08.010
15 https://doi.org/10.1016/j.ccr.2012.02.022
16 https://doi.org/10.1016/j.cell.2010.09.016
17 https://doi.org/10.1016/j.cell.2011.11.025
18 https://doi.org/10.1016/j.cell.2014.12.021
19 https://doi.org/10.1016/j.celrep.2017.09.093
20 https://doi.org/10.1016/j.cub.2014.03.059
21 https://doi.org/10.1016/j.cub.2015.12.063
22 https://doi.org/10.1016/j.devcel.2009.11.003
23 https://doi.org/10.1016/j.neo.2016.08.009
24 https://doi.org/10.1016/j.stem.2014.06.019
25 https://doi.org/10.1016/s1535-6108(03)00309-x
26 https://doi.org/10.1038/emboj.2013.204
27 https://doi.org/10.1053/j.gastro.2011.04.043
28 https://doi.org/10.1083/jcb.130.3.613
29 https://doi.org/10.1083/jcb.146.1.149
30 https://doi.org/10.1083/jcb.201202108
31 https://doi.org/10.1084/jem.20162024
32 https://doi.org/10.1088/2057-1739/2/3/035004
33 https://doi.org/10.1093/cvr/cvq144
34 https://doi.org/10.1098/rstb.2015.0520
35 https://doi.org/10.1101/gad.249409.114
36 https://doi.org/10.1101/gad.943001
37 https://doi.org/10.1103/physreve.96.032404
38 https://doi.org/10.1103/revmodphys.85.1143
39 https://doi.org/10.1126/scisignal.aaa8859
40 https://doi.org/10.1152/ajpendo.00321.2002
41 https://doi.org/10.1158/0008-5472.can-13-1911
42 https://doi.org/10.1172/jci29988
43 https://doi.org/10.1172/jci57131
44 https://doi.org/10.1242/dev.090159
45 https://doi.org/10.1242/dev.151282
46 https://doi.org/10.15252/embr.201439246
47 schema:datePublished 2019-02
48 schema:datePublishedReg 2019-02-01
49 schema:description Tubular epithelia are a basic building block of organs and a common site of cancer occurrence<sup>1-4</sup>. During tumorigenesis, transformed cells overproliferate and epithelial architecture is disrupted. However, the biophysical parameters that underlie the adoption of abnormal tumour tissue shapes are unknown. Here we show in the pancreas of mice that the morphology of epithelial tumours is determined by the interplay of cytoskeletal changes in transformed cells and the existing tubular geometry. To analyse the morphological changes in tissue architecture during the initiation of cancer, we developed a three-dimensional whole-organ imaging technique that enables tissue analysis at single-cell resolution. Oncogenic transformation of pancreatic ducts led to two types of neoplastic growth: exophytic lesions that expanded outwards from the duct and endophytic lesions that grew inwards to the ductal lumen. Myosin activity was higher apically than basally in wild-type cells, but upon transformation this gradient was lost in both lesion types. Three-dimensional vertex model simulations and a continuum theory of epithelial mechanics, which incorporate the cytoskeletal changes observed in transformed cells, indicated that the diameter of the source epithelium instructs the morphology of growing tumours. Three-dimensional imaging revealed that-consistent with theory predictions-small pancreatic ducts produced exophytic growth, whereas large ducts deformed endophytically. Similar patterns of lesion growth were observed in tubular epithelia of the liver and lung; this finding identifies tension imbalance and tissue curvature as fundamental determinants of epithelial tumorigenesis.
50 schema:genre research_article
51 schema:inLanguage en
52 schema:isAccessibleForFree false
53 schema:isPartOf N9246d24d545449659e55fc0f42c8f5dc
54 N93b29daa88fb4d9194c8bc8ee26b3196
55 sg:journal.1018957
56 schema:name Tissue curvature and apicobasal mechanical tension imbalance instruct cancer morphogenesis
57 schema:pagination 126-130
58 schema:productId N47c7c96dc5ff4ce8812d8cd12ad3d0a7
59 N694532c42f1748478eff105b7d7a6ea1
60 N8702d8a259994de6bf19a19d9405cfed
61 Na5f07aca30c844c98fdfc9543c91f9a2
62 Ncfafc9a40367400e9ccfcc61d7dfcea5
63 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111779575
64 https://doi.org/10.1038/s41586-019-0891-2
65 schema:sdDatePublished 2019-04-11T12:57
66 schema:sdLicense https://scigraph.springernature.com/explorer/license/
67 schema:sdPublisher Ne74a6926deda44c8b0587b6c9c68c492
68 schema:url https://www.nature.com/articles/s41586-019-0891-2
69 sgo:license sg:explorer/license/
70 sgo:sdDataset articles
71 rdf:type schema:ScholarlyArticle
72 N00c5fed8292e498c92312a10bac826b6 schema:affiliation https://www.grid.ac/institutes/grid.13097.3c
73 schema:familyName Behrens
74 schema:givenName Axel
75 rdf:type schema:Person
76 N0a36507d288a411f8800e35b41151f9b rdf:first N98239ae5776d41d8b5dcb27c7c338730
77 rdf:rest N56ec8d7507d242ce8934d97fff135c25
78 N12734d9338244a75807f56e753a751a9 schema:affiliation https://www.grid.ac/institutes/grid.451388.3
79 schema:familyName Wang
80 schema:givenName Victoria Min-Yi
81 rdf:type schema:Person
82 N185e1b48680846ca9eb81166eb14f78d rdf:first N00c5fed8292e498c92312a10bac826b6
83 rdf:rest rdf:nil
84 N2fd02592d54e498cbfa4dadc0a1b4010 rdf:first Nc43adbcfc0014cf48bdd1c5bb97fc8a8
85 rdf:rest N923b8e718bf3494eb56305e946bc6848
86 N30bdfb4a9b11415d9b37a9014b069a77 rdf:first N12734d9338244a75807f56e753a751a9
87 rdf:rest Nda603ec3b97f4d0c8dd18bd176803a69
88 N31b1236b30b245b1814271f86c8ac8ee schema:affiliation https://www.grid.ac/institutes/grid.451388.3
89 schema:familyName Salbreux
90 schema:givenName Guillaume
91 rdf:type schema:Person
92 N47c7c96dc5ff4ce8812d8cd12ad3d0a7 schema:name dimensions_id
93 schema:value pub.1111779575
94 rdf:type schema:PropertyValue
95 N4956422d343b4751929d7b19f45230ea schema:affiliation https://www.grid.ac/institutes/grid.451388.3
96 schema:familyName Gribben
97 schema:givenName Christopher
98 rdf:type schema:Person
99 N56ec8d7507d242ce8934d97fff135c25 rdf:first N4956422d343b4751929d7b19f45230ea
100 rdf:rest N30bdfb4a9b11415d9b37a9014b069a77
101 N694532c42f1748478eff105b7d7a6ea1 schema:name readcube_id
102 schema:value e1dd841c5587168946ca8b1ceafc84db35b80e4276f79fde2efda71d9f0cded9
103 rdf:type schema:PropertyValue
104 N71352edeef4740288cc88319cd2fb670 schema:affiliation https://www.grid.ac/institutes/grid.419491.0
105 schema:familyName Alt
106 schema:givenName Silvanus
107 rdf:type schema:Person
108 N76564a60341143ef85e1d3bc96da6d23 rdf:first N31b1236b30b245b1814271f86c8ac8ee
109 rdf:rest N185e1b48680846ca9eb81166eb14f78d
110 N8702d8a259994de6bf19a19d9405cfed schema:name doi
111 schema:value 10.1038/s41586-019-0891-2
112 rdf:type schema:PropertyValue
113 N923b8e718bf3494eb56305e946bc6848 rdf:first N71352edeef4740288cc88319cd2fb670
114 rdf:rest N0a36507d288a411f8800e35b41151f9b
115 N9246d24d545449659e55fc0f42c8f5dc schema:volumeNumber 566
116 rdf:type schema:PublicationVolume
117 N93b29daa88fb4d9194c8bc8ee26b3196 schema:issueNumber 7742
118 rdf:type schema:PublicationIssue
119 N98239ae5776d41d8b5dcb27c7c338730 schema:affiliation https://www.grid.ac/institutes/grid.83440.3b
120 schema:familyName Ferreira
121 schema:givenName Rute M. M.
122 rdf:type schema:Person
123 Na5f07aca30c844c98fdfc9543c91f9a2 schema:name nlm_unique_id
124 schema:value 0410462
125 rdf:type schema:PropertyValue
126 Nc43adbcfc0014cf48bdd1c5bb97fc8a8 schema:affiliation https://www.grid.ac/institutes/grid.451388.3
127 schema:familyName Messal
128 schema:givenName Hendrik A.
129 rdf:type schema:Person
130 Nc86f1d6a0eb4484fb8e4aa7d5a48fde5 schema:affiliation https://www.grid.ac/institutes/grid.426108.9
131 schema:familyName Cotoi
132 schema:givenName Corina G.
133 rdf:type schema:Person
134 Ncfafc9a40367400e9ccfcc61d7dfcea5 schema:name pubmed_id
135 schema:value 30700911
136 rdf:type schema:PropertyValue
137 Nda603ec3b97f4d0c8dd18bd176803a69 rdf:first Nc86f1d6a0eb4484fb8e4aa7d5a48fde5
138 rdf:rest N76564a60341143ef85e1d3bc96da6d23
139 Ne74a6926deda44c8b0587b6c9c68c492 schema:name Springer Nature - SN SciGraph project
140 rdf:type schema:Organization
141 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
142 schema:name Medical and Health Sciences
143 rdf:type schema:DefinedTerm
144 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
145 schema:name Oncology and Carcinogenesis
146 rdf:type schema:DefinedTerm
147 sg:journal.1018957 schema:issn 0090-0028
148 1476-4687
149 schema:name Nature
150 rdf:type schema:Periodical
151 sg:pub.10.1038/ncb3092 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004570820
152 https://doi.org/10.1038/ncb3092
153 rdf:type schema:CreativeWork
154 sg:pub.10.1038/ncb3246 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028738506
155 https://doi.org/10.1038/ncb3246
156 rdf:type schema:CreativeWork
157 sg:pub.10.1038/nn.2467 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022194277
158 https://doi.org/10.1038/nn.2467
159 rdf:type schema:CreativeWork
160 sg:pub.10.1038/nn.2644 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051495272
161 https://doi.org/10.1038/nn.2644
162 rdf:type schema:CreativeWork
163 sg:pub.10.1038/nphys3224 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002387502
164 https://doi.org/10.1038/nphys3224
165 rdf:type schema:CreativeWork
166 sg:pub.10.1038/onc.2015.441 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049305989
167 https://doi.org/10.1038/onc.2015.441
168 rdf:type schema:CreativeWork
169 sg:pub.10.1186/1471-213x-1-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042905963
170 https://doi.org/10.1186/1471-213x-1-4
171 rdf:type schema:CreativeWork
172 https://app.dimensions.ai/details/publication/pub.1074630051 schema:CreativeWork
173 https://doi.org/10.1002/dvg.20397 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025936015
174 rdf:type schema:CreativeWork
175 https://doi.org/10.1016/j.ccell.2016.09.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017556468
176 rdf:type schema:CreativeWork
177 https://doi.org/10.1016/j.ccr.2005.08.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038845984
178 rdf:type schema:CreativeWork
179 https://doi.org/10.1016/j.ccr.2012.02.022 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002516265
180 rdf:type schema:CreativeWork
181 https://doi.org/10.1016/j.cell.2010.09.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043020547
182 rdf:type schema:CreativeWork
183 https://doi.org/10.1016/j.cell.2011.11.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032774444
184 rdf:type schema:CreativeWork
185 https://doi.org/10.1016/j.cell.2014.12.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024162945
186 rdf:type schema:CreativeWork
187 https://doi.org/10.1016/j.celrep.2017.09.093 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092348715
188 rdf:type schema:CreativeWork
189 https://doi.org/10.1016/j.cub.2014.03.059 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031757440
190 rdf:type schema:CreativeWork
191 https://doi.org/10.1016/j.cub.2015.12.063 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002758530
192 rdf:type schema:CreativeWork
193 https://doi.org/10.1016/j.devcel.2009.11.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028326990
194 rdf:type schema:CreativeWork
195 https://doi.org/10.1016/j.neo.2016.08.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048945830
196 rdf:type schema:CreativeWork
197 https://doi.org/10.1016/j.stem.2014.06.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007013021
198 rdf:type schema:CreativeWork
199 https://doi.org/10.1016/s1535-6108(03)00309-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1012489329
200 rdf:type schema:CreativeWork
201 https://doi.org/10.1038/emboj.2013.204 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046241891
202 rdf:type schema:CreativeWork
203 https://doi.org/10.1053/j.gastro.2011.04.043 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032119464
204 rdf:type schema:CreativeWork
205 https://doi.org/10.1083/jcb.130.3.613 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019982175
206 rdf:type schema:CreativeWork
207 https://doi.org/10.1083/jcb.146.1.149 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011427771
208 rdf:type schema:CreativeWork
209 https://doi.org/10.1083/jcb.201202108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034402475
210 rdf:type schema:CreativeWork
211 https://doi.org/10.1084/jem.20162024 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083862081
212 rdf:type schema:CreativeWork
213 https://doi.org/10.1088/2057-1739/2/3/035004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059183609
214 rdf:type schema:CreativeWork
215 https://doi.org/10.1093/cvr/cvq144 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027797834
216 rdf:type schema:CreativeWork
217 https://doi.org/10.1098/rstb.2015.0520 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084197262
218 rdf:type schema:CreativeWork
219 https://doi.org/10.1101/gad.249409.114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048897105
220 rdf:type schema:CreativeWork
221 https://doi.org/10.1101/gad.943001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007211161
222 rdf:type schema:CreativeWork
223 https://doi.org/10.1103/physreve.96.032404 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091497624
224 rdf:type schema:CreativeWork
225 https://doi.org/10.1103/revmodphys.85.1143 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060839747
226 rdf:type schema:CreativeWork
227 https://doi.org/10.1126/scisignal.aaa8859 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022665209
228 rdf:type schema:CreativeWork
229 https://doi.org/10.1152/ajpendo.00321.2002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022745317
230 rdf:type schema:CreativeWork
231 https://doi.org/10.1158/0008-5472.can-13-1911 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021894849
232 rdf:type schema:CreativeWork
233 https://doi.org/10.1172/jci29988 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019516471
234 rdf:type schema:CreativeWork
235 https://doi.org/10.1172/jci57131 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041825328
236 rdf:type schema:CreativeWork
237 https://doi.org/10.1242/dev.090159 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021220233
238 rdf:type schema:CreativeWork
239 https://doi.org/10.1242/dev.151282 schema:sameAs https://app.dimensions.ai/details/publication/pub.1093048940
240 rdf:type schema:CreativeWork
241 https://doi.org/10.15252/embr.201439246 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002160543
242 rdf:type schema:CreativeWork
243 https://www.grid.ac/institutes/grid.13097.3c schema:alternateName King's College London
244 schema:name Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK
245 Faculty of Life Sciences and Medicine, King’s College London, London, UK
246 rdf:type schema:Organization
247 https://www.grid.ac/institutes/grid.419491.0 schema:alternateName Max Delbrück Center for Molecular Medicine
248 schema:name Max Delbrück Center for Molecular Medicine, Berlin, Germany
249 Theoretical Physics of Biology Laboratory, The Francis Crick Institute, London, UK
250 rdf:type schema:Organization
251 https://www.grid.ac/institutes/grid.426108.9 schema:alternateName Royal Free Hospital
252 schema:name Department of Cellular Pathology, The Royal Free Hospital, London, UK
253 Institute of Liver Studies, King’s College Hospital, London, UK
254 rdf:type schema:Organization
255 https://www.grid.ac/institutes/grid.451388.3 schema:alternateName The Francis Crick Institute
256 schema:name Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK
257 Theoretical Physics of Biology Laboratory, The Francis Crick Institute, London, UK
258 rdf:type schema:Organization
259 https://www.grid.ac/institutes/grid.83440.3b schema:alternateName University College London
260 schema:name Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK
261 Cell Death, Cancer and Inflammation Laboratory, University College London Cancer Institute, London, UK
262 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...