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Downregulation of E...
Downregulation of Epidermal Growth Factor Receptor in hepatocellular carcinoma facilitates Transforming Growth Factor-beta-induced epithelial to amoeboid transition
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- Lopez-Luque, Judit (author)
- Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, TGP B, Barcelona, Spain;Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, Canc Grp, Barcelona, Spain;Inst Salud Carlos III, Oncol Program, CIBEREHD, Natl Biomed Res Inst Liver & Gastrointestinal Dis, Madrid, Spain
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- Bertran, Esther (author)
- Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, TGP B, Barcelona, Spain;Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, Canc Grp, Barcelona, Spain;Inst Salud Carlos III, Oncol Program, CIBEREHD, Natl Biomed Res Inst Liver & Gastrointestinal Dis, Madrid, Spain
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- Crosas-Molist, Eva (author)
- Queen Mary Univ London, Barts Canc Inst, Canc Res UK Ctr Excellence, John Vane Sci Bldg Charterhouse Sq, London EC1M 6BQ, England
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- Maiques, Oscar (author)
- Queen Mary Univ London, Barts Canc Inst, Canc Res UK Ctr Excellence, John Vane Sci Bldg Charterhouse Sq, London EC1M 6BQ, England
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- Malfettone, Andrea (author)
- Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, TGP B, Barcelona, Spain;Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, Canc Grp, Barcelona, Spain
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- Caja, Laia (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Serrano, Teresa (author)
- Inst Salud Carlos III, Oncol Program, CIBEREHD, Natl Biomed Res Inst Liver & Gastrointestinal Dis, Madrid, Spain;Univ Hosp Bellvitge, Pathol Anat Serv, Barcelona, Spain
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- Ramos, Emilio (author)
- Inst Salud Carlos III, Oncol Program, CIBEREHD, Natl Biomed Res Inst Liver & Gastrointestinal Dis, Madrid, Spain;Univ Hosp Bellvitge, Liver Transplant Unit, Dept Surg, Barcelona, Spain
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- Sanz-Moreno, Victoria (author)
- Queen Mary Univ London, Barts Canc Inst, Canc Res UK Ctr Excellence, John Vane Sci Bldg Charterhouse Sq, London EC1M 6BQ, England
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- Fabregat, Isabel (author)
- Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, TGP B, Barcelona, Spain;Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, Canc Grp, Barcelona, Spain;Inst Salud Carlos III, Oncol Program, CIBEREHD, Natl Biomed Res Inst Liver & Gastrointestinal Dis, Madrid, Spain;Univ Barcelona, Fac Med & Hlth Sci, Dept Physiol Sci, Barcelona, Spain
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(creator_code:org_t)
- ELSEVIER IRELAND LTD, 2019
- 2019
- English.
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In: Cancer Letters. - : ELSEVIER IRELAND LTD. - 0304-3835 .- 1872-7980. ; 464:Nov, s. 15-24
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Abstract
Subject headings
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- The Epidermal Growth Factor Receptor (EGFR) and the Transforming Growth Factor-beta (TGF-beta) are key regulators of hepatocarcinogenesis. Targeting EGFR was proposed as a promising therapy; however, poor success was obtained in human hepatocellular carcinoma (HCC) clinical trials. Here, we describe how EGFR is frequently downregulated in HCC patients while TGF-beta is upregulated. Using 2D/3D cellular models, we show that after EGFR loss, TGF-beta is more efficient in its pro-migratory and invasive effects, inducing epithelial to amoeboid transition. EGFR knock-down promotes loss of cell-cell and cell-to-matrix adhesion, favouring TGF-beta-induced actomyosin contractility and acquisition of an amoeboid migratory phenotype. Moreover, TGF-beta upregulates RHOC and CDC42 after EGFR silencing, promoting Myosin II in amoeboid cells. Importantly, low EGFR combined with high TGFBI or RHOC/CDC42 levels confer poor patient prognosis. In conclusion, this work reveals a new tumour suppressor function for EGFR counteracting TGF-beta-mediated epithelial to amoeboid transitions in HCC, supporting a rational for targeting the TGF-beta pathway in patients with low EGFR expression. Our work also highlights the relevance of epithelial to amoeboid transition in human tumours and the need to better target this process in the clinic.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Liver
- Migration
- Adhesion
- Matrix
- Myosin II
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lopez-Luque, Jud ...
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Bertran, Esther
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Crosas-Molist, E ...
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Maiques, Oscar
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Malfettone, Andr ...
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Caja, Laia
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Serrano, Teresa
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Ramos, Emilio
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Sanz-Moreno, Vic ...
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Fabregat, Isabel
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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 Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Letters
- By the university
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Uppsala University