ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1563969
ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity
Provisionally accepted
Sofia Morazzo1,2
Soraia Fernandes1Marina Fortea3Helena Skálová1
Marco Cassani1Kamila Vrzalová1,4Filip Kafka1,2
Jan Vrbsky1
Daniel Pereira-Sousa1,2
Veronika Bosáková1,2Jaeyoung Shin5
Jan Fric1,6,7
Kristina Haase3
Giancarlo Forte1,8*- 1International Clinical Research Center (FNUSA-ICRC), Brno, Czechia
- 2Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czechia
- 3European Molecular Biology Laboratory Barcelona, Span, Spain
- 4Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czechia
- 5AtoGen Co., Ltd., Daejeon, Republic of Korea
- 6Institute of Haematology and Blood Transfusion (Czechia), Prague, Prague, Czechia
- 7International Clinical Research Center (ICRC), Faculty of Medicine, Masaryk University, Brno, Czechia
- 8School of Cardiovascular and Metabolic Medicine & Sciences, King’s College London, London, England, United Kingdom
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Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. In breast cancer cells, epithelial-to-mesenchymal transition (EMT) plasticity is required for successful metastasis. ERK3 has been implicated in promoting breast cancer migration and invasion, but the mechanisms remain elusive. Here, we investigated ERK3 expression across patient-derived datasets and established its association with aggressive breast cancer phenotypes, higher tumour plasticity collated to its grade and poor clinical outcomes. Based on the hypothesis that ERK3 contributes to TNBC progression by supporting a partial-EMT state, we showed that ERK3 is essential in different steps of the metastatic process, especially by enabling collective migration but also by modulating cell-extracellular matrix adhesion, anchorage-independent growth, extravasation and colonization. In conclusion, our results demonstrate that ERK3 contributes to TNBC progression and potentially metastasis by promoting EMT plasticity and collective migration.
Keywords: Triple-negative breast cancer (TNBC), extracellular-regulated kinase 3 (ERK3), Epithelial-to-mesenchymal transition (EMT), Epithelial-mesenchymal plasticity (EMP), collective migration
Received: 20 Jan 2025; Accepted: 11 Jul 2025.
Copyright: © 2025 Morazzo, Fernandes, Fortea, Skálová, Cassani, Vrzalová, Kafka, Vrbsky, Pereira-Sousa, Bosáková, Shin, Fric, Haase and Forte. 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) or licensor 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.
* Correspondence: Giancarlo Forte, International Clinical Research Center (FNUSA-ICRC), Brno, Czechia
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