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Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway

Some yet unidentified factors released by both oocyte and embryonic microenvironments demonstrated to be non-permissive for tumor development and display the remarkable ability to foster cell/tissue reprogramming, thus ultimately reversing the malignant phenotype. In the present study we observed ho...

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Autores principales: Proietti, Sara, Cucina, Alessandra, Pensotti, Andrea, Biava, Pier Mario, Minini, Mirko, Monti, Noemi, Catizone, Angela, Ricci, Giulia, Leonetti, Erica, Harrath, Abdel Halim, Alwasel, Saleh H., Bizzarri, Mariano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539734/
https://www.ncbi.nlm.nih.gov/pubmed/31052313
http://dx.doi.org/10.3390/ijms20092151
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author Proietti, Sara
Cucina, Alessandra
Pensotti, Andrea
Biava, Pier Mario
Minini, Mirko
Monti, Noemi
Catizone, Angela
Ricci, Giulia
Leonetti, Erica
Harrath, Abdel Halim
Alwasel, Saleh H.
Bizzarri, Mariano
author_facet Proietti, Sara
Cucina, Alessandra
Pensotti, Andrea
Biava, Pier Mario
Minini, Mirko
Monti, Noemi
Catizone, Angela
Ricci, Giulia
Leonetti, Erica
Harrath, Abdel Halim
Alwasel, Saleh H.
Bizzarri, Mariano
author_sort Proietti, Sara
collection PubMed
description Some yet unidentified factors released by both oocyte and embryonic microenvironments demonstrated to be non-permissive for tumor development and display the remarkable ability to foster cell/tissue reprogramming, thus ultimately reversing the malignant phenotype. In the present study we observed how molecular factors extracted from Zebrafish embryos during specific developmental phases (20 somites) significantly antagonize proliferation of breast cancer cells, while reversing a number of prominent aspects of malignancy. Embryo extracts reduce cell proliferation, enhance apoptosis, and dramatically inhibit both invasiveness and migrating capabilities of cancer cells. Counteracting the invasive phenotype is a relevant issue in controlling tumor spreading and metastasis. Moreover, such effect is not limited to cancerous cells as embryo extracts were also effective in inhibiting migration and invasiveness displayed by normal breast cells undergoing epithelial–mesenchymal transition upon TGF-β1 stimulation. The reversion program involves the modulation of E-cadherin/β-catenin pathway, cytoskeleton remodeling with dramatic reduction in vinculin, as well as downregulation of TCTP and the concomitant increase in p53 levels. Our findings highlight that—contrary to the prevailing current “dogma”, which posits that neoplastic cells are irreversibly “committed”—the malignant phenotype can ultimately be “reversed”, at least partially, in response to environmental morphogenetic influences.
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spelling pubmed-65397342019-06-04 Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway Proietti, Sara Cucina, Alessandra Pensotti, Andrea Biava, Pier Mario Minini, Mirko Monti, Noemi Catizone, Angela Ricci, Giulia Leonetti, Erica Harrath, Abdel Halim Alwasel, Saleh H. Bizzarri, Mariano Int J Mol Sci Article Some yet unidentified factors released by both oocyte and embryonic microenvironments demonstrated to be non-permissive for tumor development and display the remarkable ability to foster cell/tissue reprogramming, thus ultimately reversing the malignant phenotype. In the present study we observed how molecular factors extracted from Zebrafish embryos during specific developmental phases (20 somites) significantly antagonize proliferation of breast cancer cells, while reversing a number of prominent aspects of malignancy. Embryo extracts reduce cell proliferation, enhance apoptosis, and dramatically inhibit both invasiveness and migrating capabilities of cancer cells. Counteracting the invasive phenotype is a relevant issue in controlling tumor spreading and metastasis. Moreover, such effect is not limited to cancerous cells as embryo extracts were also effective in inhibiting migration and invasiveness displayed by normal breast cells undergoing epithelial–mesenchymal transition upon TGF-β1 stimulation. The reversion program involves the modulation of E-cadherin/β-catenin pathway, cytoskeleton remodeling with dramatic reduction in vinculin, as well as downregulation of TCTP and the concomitant increase in p53 levels. Our findings highlight that—contrary to the prevailing current “dogma”, which posits that neoplastic cells are irreversibly “committed”—the malignant phenotype can ultimately be “reversed”, at least partially, in response to environmental morphogenetic influences. MDPI 2019-04-30 /pmc/articles/PMC6539734/ /pubmed/31052313 http://dx.doi.org/10.3390/ijms20092151 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Proietti, Sara
Cucina, Alessandra
Pensotti, Andrea
Biava, Pier Mario
Minini, Mirko
Monti, Noemi
Catizone, Angela
Ricci, Giulia
Leonetti, Erica
Harrath, Abdel Halim
Alwasel, Saleh H.
Bizzarri, Mariano
Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway
title Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway
title_full Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway
title_fullStr Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway
title_full_unstemmed Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway
title_short Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-Regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway
title_sort active fraction from embryo fish extracts induces reversion of the malignant invasive phenotype in breast cancer through down-regulation of tctp and modulation of e-cadherin/β-catenin pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539734/
https://www.ncbi.nlm.nih.gov/pubmed/31052313
http://dx.doi.org/10.3390/ijms20092151
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