Global signalling network analysis of luminal T47D breast cancer cells in response to progesterone
Author
Wright, Roni
Vastolo, Viviana
Quilez, Javier
Carbonell Caballero, José
Beato, Miguel
Publication date
2022ISSN
1664-2392
Abstract
Background: Breast cancer cells enter into the cell cycle following progestin exposure by the activation of signalling cascades involving a plethora of enzymes, transcription factors and co-factors that transmit the external signal from the cell membrane to chromatin, ultimately leading to a change of the gene expression program. Although many of the events within the signalling network have been described in isolation, how they globally team up to generate the final cell response is unclear. Methods: In this study we used antibody microarrays and phosphoproteomics to reveal a dynamic global signalling map that reveals new key regulated proteins and phosphor-sites and links between previously known and novel pathways. T47D breast cancer cells were used, and phospho-sites and pathways highlighted were validated using specific antibodies and phenotypic assays. Bioinformatic analysis revealed an enrichment in novel signalling pathways, a coordinated response between cellular compartments and protein complexes. Results: Detailed analysis of the data revealed intriguing changes in protein complexes involved in nuclear structure, epithelial to mesenchyme transition (EMT), cell adhesion, as well as transcription factors previously not associated with breast cancer cell proliferation. Pathway analysis confirmed the key role of the MAPK signalling cascade following progesterone and additional hormone regulated phospho-sites were identified. Full network analysis shows the activation of new signalling pathways previously not associated with progesterone signalling in T47D breast cancer cells such as ERBB and TRK. As different post-translational modifications can mediate complex crosstalk mechanisms and massive PARylation is also rapidly induced by progestins, we provide details of important chromatin regulatory complexes containing both phosphorylated and PARylated proteins. Conclusions: This study contributes an important resource for the scientific community, as it identifies novel players and connections meaningful for breast cancer cell biology and potentially relevant for cancer management.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
616 - Pathology. Clinical medicine
Keywords
Progesterona
Càncer de mama
Fosfoproteoma
Senyalització
Senyalització MAPK/ERK
Cromatina
PARilació
Proliferació cel·lular
Progesterona
Cáncer de mama
Fosfoproteoma
Señalización
Señalización MAPK/ERK
Cromatina
PARilación
Proliferación celular
Progesterone
Breast cancer
Phosphoproteome
Signalling
MAPK/ERK signalling
Chromatin
PARylation
Cell proliferation
Pages
19
Publisher
Frontiers Media
Collection
13
Is part of
Frontiers in Endocrinology
Citation
Wright, Roni; Vastolo, Viviana; Quilez, Javier [et al.]. Global signalling network analysis of luminal T47D breast cancer cells in response to progesterone. Frontiers in Endocrinology, 2022, 13, 888802. Disponible en: <https://www.frontiersin.org/articles/10.3389/fendo.2022.888802/full>. Fecha de acceso: 20 oct. 2022. DOI: 10.3389/fendo.2022.888802
Link to the related item
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- Ciències Bàsiques [65]
Rights
© 2022 Wright, Vastolo, Oliete, Carbonell-Caballero and Beato. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/