Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783422459043643392 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6539734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT proiettisara activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT cucinaalessandra activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT pensottiandrea activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT biavapiermario activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT mininimirko activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT montinoemi activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT catizoneangela activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT riccigiulia activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT leonettierica activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT harrathabdelhalim activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT alwaselsalehh activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway AT bizzarrimariano activefractionfromembryofishextractsinducesreversionofthemalignantinvasivephenotypeinbreastcancerthroughdownregulationoftctpandmodulationofecadherinbcateninpathway |