Cargando…

New Therapeutic Approach for Targeting Hippo Signalling Pathway

Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interacti...

Descripción completa

Detalles Bibliográficos
Autores principales: Dominguez-Berrocal, Leticia, Cirri, Erica, Zhang, Xiguang, Andrini, Laura, Marin, Gustavo H., Lebel-Binay, Sophie, Rebollo, Angelita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423280/
https://www.ncbi.nlm.nih.gov/pubmed/30886324
http://dx.doi.org/10.1038/s41598-019-41404-w
_version_ 1783404505631555584
author Dominguez-Berrocal, Leticia
Cirri, Erica
Zhang, Xiguang
Andrini, Laura
Marin, Gustavo H.
Lebel-Binay, Sophie
Rebollo, Angelita
author_facet Dominguez-Berrocal, Leticia
Cirri, Erica
Zhang, Xiguang
Andrini, Laura
Marin, Gustavo H.
Lebel-Binay, Sophie
Rebollo, Angelita
author_sort Dominguez-Berrocal, Leticia
collection PubMed
description Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interaction between TEAD and YAP, two transcription factors involved in the Hippo signalling pathway, whose deregulation is related to several types of cancer. We have validated the cell penetration and nuclear localization by flow cytometry and fluorescence microscopy and shown that the new generated peptide displays an apoptotic effect in tumor cell lines thanks to the specific nuclear delivery of the cargo, which targets a protein/protein interaction in the nucleus. In addition, the peptide has an anti-tumoral effect in vivo in xenograft models of breast cancer. The chimeric peptide designed in the current study shows encouraging prospects for developing nuclear anti- neoplastic drugs.
format Online
Article
Text
id pubmed-6423280
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64232802019-03-26 New Therapeutic Approach for Targeting Hippo Signalling Pathway Dominguez-Berrocal, Leticia Cirri, Erica Zhang, Xiguang Andrini, Laura Marin, Gustavo H. Lebel-Binay, Sophie Rebollo, Angelita Sci Rep Article Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interaction between TEAD and YAP, two transcription factors involved in the Hippo signalling pathway, whose deregulation is related to several types of cancer. We have validated the cell penetration and nuclear localization by flow cytometry and fluorescence microscopy and shown that the new generated peptide displays an apoptotic effect in tumor cell lines thanks to the specific nuclear delivery of the cargo, which targets a protein/protein interaction in the nucleus. In addition, the peptide has an anti-tumoral effect in vivo in xenograft models of breast cancer. The chimeric peptide designed in the current study shows encouraging prospects for developing nuclear anti- neoplastic drugs. Nature Publishing Group UK 2019-03-18 /pmc/articles/PMC6423280/ /pubmed/30886324 http://dx.doi.org/10.1038/s41598-019-41404-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dominguez-Berrocal, Leticia
Cirri, Erica
Zhang, Xiguang
Andrini, Laura
Marin, Gustavo H.
Lebel-Binay, Sophie
Rebollo, Angelita
New Therapeutic Approach for Targeting Hippo Signalling Pathway
title New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_full New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_fullStr New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_full_unstemmed New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_short New Therapeutic Approach for Targeting Hippo Signalling Pathway
title_sort new therapeutic approach for targeting hippo signalling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423280/
https://www.ncbi.nlm.nih.gov/pubmed/30886324
http://dx.doi.org/10.1038/s41598-019-41404-w
work_keys_str_mv AT dominguezberrocalleticia newtherapeuticapproachfortargetinghipposignallingpathway
AT cirrierica newtherapeuticapproachfortargetinghipposignallingpathway
AT zhangxiguang newtherapeuticapproachfortargetinghipposignallingpathway
AT andrinilaura newtherapeuticapproachfortargetinghipposignallingpathway
AT maringustavoh newtherapeuticapproachfortargetinghipposignallingpathway
AT lebelbinaysophie newtherapeuticapproachfortargetinghipposignallingpathway
AT rebolloangelita newtherapeuticapproachfortargetinghipposignallingpathway