Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway

Treatment for the HER2+ breast cancer subtype is still unsatisfactory, despite breakthroughs in research. The discovery of various new molecular mechanisms of transcription factors may help to make treatment regimens more effective. The transcription factor SALL4 has been related to aggressiveness a...

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Detalhes bibliográficos
Autores: Pattanayak, Birlipta, Lameirinhas, Ana, Torres-Ruiz, Sandra, Burgués, Octavio, Rovira, Ana, Martínez, María Teresa, Tapia, Marta, Zazo, Sandra, Albanell Mestres, Joan, Rojo, Federico, Bermejo, Begoña, Eroles, Pilar
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/56454
Acesso em linha:http://hdl.handle.net/10230/56454
http://dx.doi.org/10.3390/ijms232113292
Access Level:acceso abierto
Palavra-chave:EMT
HER2+ breast cancer
PI3K/AKT pathway
SALL4
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spelling Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathwayPattanayak, BirliptaLameirinhas, AnaTorres-Ruiz, SandraBurgués, OctavioRovira, AnaMartínez, María TeresaTapia, MartaZazo, SandraAlbanell Mestres, JoanRojo, FedericoBermejo, BegoñaEroles, PilarEMTHER2+ breast cancerPI3K/AKT pathwaySALL4Treatment for the HER2+ breast cancer subtype is still unsatisfactory, despite breakthroughs in research. The discovery of various new molecular mechanisms of transcription factors may help to make treatment regimens more effective. The transcription factor SALL4 has been related to aggressiveness and resistance therapy in cancer. Its molecular mechanisms and involvement in various signaling pathways are unknown in the HER2+ breast cancer subtype. In this study, we have evaluated the implication of SALL4 in the HER2+ subtype through its expression in patients' samples and gain and loss of function in HER2+ cell lines. We found higher SALL4 expression in breast cancer tissues compared to healthy tissue. Interestingly, high SALL4 expression was associated with disease relapse and poor patient survival. In HER2+ cell lines, transient overexpression of SALL4 modulates PI3K/AKT signaling through regulating PTEN expression and BCL2, which increases cell survival and proliferation while reducing the efficacy of trastuzumab. SALL4 has also been observed to regulate the epithelial-mesenchymal transition and stemness features. SALL4 overexpression significantly reduced the epithelial markers E-cadherin, while it increased the mesenchymal markers β-catenin, vimentin and fibronectin. Furthermore, it has been also observed an increased expression of MYC, an essential transcription factor for regulating epithelial-mesenchymal transition and/or cancer stem cells. Our study demonstrates, for the first time, the importance of SALL4 in the HER2+ subtype and partial regulation of trastuzumab sensitivity. It provides a viable molecular mechanism-driven therapeutic strategy for an important subset of HER2-overexpressing patients whose malignancies are mediated by SALL4 expression.MDPI202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/56454http://dx.doi.org/10.3390/ijms232113292reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésInt J Mol Sci. 2022 Oct 31;23(21):13292© 2022 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 (https://creativecommons.org/licenses/by/4.0/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/564542026-06-12T07:21:37Z
dc.title.none.fl_str_mv Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
title Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
spellingShingle Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
Pattanayak, Birlipta
EMT
HER2+ breast cancer
PI3K/AKT pathway
SALL4
title_short Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
title_full Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
title_fullStr Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
title_full_unstemmed Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
title_sort Role of SALL4 in HER2+ breast cancer progression: Regulating PI3K/AKT pathway
dc.creator.none.fl_str_mv Pattanayak, Birlipta
Lameirinhas, Ana
Torres-Ruiz, Sandra
Burgués, Octavio
Rovira, Ana
Martínez, María Teresa
Tapia, Marta
Zazo, Sandra
Albanell Mestres, Joan
Rojo, Federico
Bermejo, Begoña
Eroles, Pilar
author Pattanayak, Birlipta
author_facet Pattanayak, Birlipta
Lameirinhas, Ana
Torres-Ruiz, Sandra
Burgués, Octavio
Rovira, Ana
Martínez, María Teresa
Tapia, Marta
Zazo, Sandra
Albanell Mestres, Joan
Rojo, Federico
Bermejo, Begoña
Eroles, Pilar
author_role author
author2 Lameirinhas, Ana
Torres-Ruiz, Sandra
Burgués, Octavio
Rovira, Ana
Martínez, María Teresa
Tapia, Marta
Zazo, Sandra
Albanell Mestres, Joan
Rojo, Federico
Bermejo, Begoña
Eroles, Pilar
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EMT
HER2+ breast cancer
PI3K/AKT pathway
SALL4
topic EMT
HER2+ breast cancer
PI3K/AKT pathway
SALL4
description Treatment for the HER2+ breast cancer subtype is still unsatisfactory, despite breakthroughs in research. The discovery of various new molecular mechanisms of transcription factors may help to make treatment regimens more effective. The transcription factor SALL4 has been related to aggressiveness and resistance therapy in cancer. Its molecular mechanisms and involvement in various signaling pathways are unknown in the HER2+ breast cancer subtype. In this study, we have evaluated the implication of SALL4 in the HER2+ subtype through its expression in patients' samples and gain and loss of function in HER2+ cell lines. We found higher SALL4 expression in breast cancer tissues compared to healthy tissue. Interestingly, high SALL4 expression was associated with disease relapse and poor patient survival. In HER2+ cell lines, transient overexpression of SALL4 modulates PI3K/AKT signaling through regulating PTEN expression and BCL2, which increases cell survival and proliferation while reducing the efficacy of trastuzumab. SALL4 has also been observed to regulate the epithelial-mesenchymal transition and stemness features. SALL4 overexpression significantly reduced the epithelial markers E-cadherin, while it increased the mesenchymal markers β-catenin, vimentin and fibronectin. Furthermore, it has been also observed an increased expression of MYC, an essential transcription factor for regulating epithelial-mesenchymal transition and/or cancer stem cells. Our study demonstrates, for the first time, the importance of SALL4 in the HER2+ subtype and partial regulation of trastuzumab sensitivity. It provides a viable molecular mechanism-driven therapeutic strategy for an important subset of HER2-overexpressing patients whose malignancies are mediated by SALL4 expression.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/56454
http://dx.doi.org/10.3390/ijms232113292
url http://hdl.handle.net/10230/56454
http://dx.doi.org/10.3390/ijms232113292
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Int J Mol Sci. 2022 Oct 31;23(21):13292
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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