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CXADR-Mediated Form...
CXADR-Mediated Formation of an AKT Inhibitory Signalosome at Tight Junctions Controls Epithelial-Mesenchymal Plasticity in Breast Cancer.
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- Nilchian, Azadeh (author)
- Karolinska Institutet
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- Johansson, Joel (author)
- Karolinska Institutet
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- Ghalali, Aram (author)
- Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA
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- Travica Asanin, Sandra (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden
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- Santiago, Ana (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden
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- Rosencrantz, Oskar (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden
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- Vincent, C. Theresa (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden;Weill Cornell Med, Dept Physiol & Biophys, New York, NY USA
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- Sollerbrant, Kerstin (author)
- Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Univ Hosp, Stockholm, Sweden
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- Sund, Malin (author)
- Umeå universitet,Kirurgi,Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden
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- Stenius, Ulla (author)
- Karolinska Institutet
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- Fuxe, Jonas (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden
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(creator_code:org_t)
- American Association for Cancer Research, 2019
- 2019
- English.
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In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 79:1, s. 47-60
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Tight junctions (TJ) act as hubs for intracellular signaling pathways controlling epithelial cell fate and function. Deregulation of TJ is a hallmark of epithelial-mesenchymal transition (EMT), which contributes to carcinoma progression and metastasis. However, the signaling mechanisms linking TJ to the induction of EMT are not understood. Here we identify a TJ-based signalosome, which controls AKT signaling and EMT in breast cancer. The coxsackie- and adenovirus receptor (CXADR), a TJ protein with an essential yet uncharacterized role in organogenesis and tissue homeostasis, was identified as a key component of the signalosome. CXADR regulated the stability and function of the phosphatases and AKT inhibitors PTEN and PHLPP2. Loss of CXADR led to hyper-activation of AKT and sensitized cells to TGF-β1-induced EMT. Conversely, restoration of CXADR stabilized PHLPP2 and PTEN, inhibited AKT, and promoted epithelial differentiation. Loss of CXADR in luminal A breast cancer correlated with loss of PHLPP2 and PTEN and poor prognosis. These results show that CXADR promotes the formation of an AKT-inhibitory signalosome at TJ and regulates epithelial-mesenchymal plasticity in breast cancer cells. Moreover, loss of CXADR might be used as a prognostic marker in luminal breast cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- 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)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Nilchian, Azadeh
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Johansson, Joel
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Ghalali, Aram
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Travica Asanin, ...
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Santiago, Ana
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Rosencrantz, Osk ...
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show more...
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Vincent, C. Ther ...
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Sollerbrant, Ker ...
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Sund, Malin
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Stenius, Ulla
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Fuxe, Jonas
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cancer Research
- By the university
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Umeå University
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Uppsala University
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Karolinska Institutet