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E-cadherin can limit the transforming properties of activating beta-catenin mutations

Huels, David J. (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
Ridgway, Rachel A. (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
Radulescu, Sorina (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
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Leushacke, Marc (author)
ASTAR, Inst Med Biol, Singapore, Singapore.
Campbell, Andrew D. (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
Biswas, Sujata (author)
Univ Oxford, Wellcome Trust Ctr Human Genet, Gastrointestinal Stem Cell Biol Lab, Oxford, England.;John Radcliffe Hosp, Nuffield Dept Clin Med, Div Expt Med, Translat Gastroenterol Unit, Oxford OX3 9DU, Headington, England.
Leedham, Simon (author)
Univ Oxford, Wellcome Trust Ctr Human Genet, Gastrointestinal Stem Cell Biol Lab, Oxford, England.;John Radcliffe Hosp, Nuffield Dept Clin Med, Div Expt Med, Translat Gastroenterol Unit, Oxford OX3 9DU, Headington, England.
Serra, Stefano (author)
Univ Hlth Network, Toronto Med Labs, Dept Pathol, Toronto, ON, Canada.
Chetty, Runjan (author)
Univ Hlth Network, Toronto Med Labs, Dept Pathol, Toronto, ON, Canada.
Moreaux, Guenievre (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
Parry, Lee (author)
Cardiff Univ, European Canc Stem Cell Res Inst, Cardiff CF10 3AX, S Glam, Wales.
Matthews, James (author)
Cardiff Univ, European Canc Stem Cell Res Inst, Cardiff CF10 3AX, S Glam, Wales.
Song, Fei (author)
Univ Giessen, Inst Physiol, D-35390 Giessen, Germany.
Hedley, Ann (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
Kalna, Gabriela (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
Ceteci, Fatih (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
Reed, Karen R. (author)
Cardiff Univ, European Canc Stem Cell Res Inst, Cardiff CF10 3AX, S Glam, Wales.
Meniel, Valerie S. (author)
Cardiff Univ, European Canc Stem Cell Res Inst, Cardiff CF10 3AX, S Glam, Wales.
Maguire, Aoife (author)
St James Hosp, Trinity Coll Dublin, Dept Histopathol, Dublin 8, Ireland.
Doyle, Brendan (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.;St James Hosp, Trinity Coll Dublin, Dept Histopathol, Dublin 8, Ireland.
Soderberg, Ola (author)
Uppsala universitet,Molekylära verktyg
Barker, Nick (author)
ASTAR, Inst Med Biol, Singapore, Singapore.
Watson, Alastair (author)
Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England.
Larue, Lionel (author)
Inst Curie, CNRS UMR3347, INSERM, U1021,Equipe Labellisee Ligue Natl Canc, F-91405 Orsay, France.
Clarke, Alan R. (author)
Cardiff Univ, European Canc Stem Cell Res Inst, Cardiff CF10 3AX, S Glam, Wales.
Sansom, Owen J. (author)
Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
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Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland ASTAR, Inst Med Biol, Singapore, Singapore. (creator_code:org_t)
2015-08-03
2015
English.
In: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 34:18, s. 2321-2333
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Wnt pathway deregulation is a common characteristic of many cancers. Only colorectal cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of the pancreas) have activating mutations in beta-catenin (CTNNB1). We have compared the dynamics and the potency of beta-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of beta-catenin took much longer to achieve Wnt deregulation and acquire a crypt-progenitor cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of beta-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of beta-catenin mutation to differentially transform the SI versus the colon correlated with higher expression of E-cadherin and a higher number of E-cadherin: beta-catenin complexes at the membrane. Reduction in E-cadherin synergised with an activating mutation of beta-catenin resulting in a rapid CPC phenotype within the SI and colon. Thus, there is a threshold of beta-catenin that is required to drive transformation, and E-cadherin can act as a buffer to sequester mutated beta-catenin.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

APC
beta-catenin
colorectal cancer
E-cadherin

Publication and Content Type

ref (subject category)
art (subject category)

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