Unraveling the EMT Spectrum in Aggressive Breast Cancer: Bridging Molecular Hybrid States with Functional Assay Interpretation
5 affiliations
- 1Doctoral Study Program in Medical Science, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia
- 2Department of Anatomy, Anatomical Pathology, and Histology, Faculty of Medicine, Universitas Lampung, Bandar Lampung, Lampung, Indonesia
- 3Medical Profession Program in Medical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- 4Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia
- 5Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, West Java, Indonesia
Abstract
Recent evidence redefines the Epithelial-Mesenchymal Transition (EMT) from a rigid binary switch into a fluid, multidimensional spectrum. In aggressive breast cancer subtypes, particularly Triple-Negative Breast Cancer (TNBC), this plasticity gives rise to hybrid phenotypes that paradoxically co-express epithelial and mesenchymal traits. These intermediate states fuel collective cell migration and therapeutic evasion by maintaining a balance between cellular adhesion and motility. This review synthesizes current molecular insights into EMT plasticity, focusing on the interconnected regulatory networks involving core transcription factors such as SNAIL, ZEB1/2, and TWIST, alongside upstream signaling pathways like TGF-β and Wnt/β-catenin. Beyond summarizing EMT plasticity and hybrid states, this review specifically bridges the molecular EMT spectrum with the interpretation of common functional migration and invasion assays. We critically evaluate how these molecular states may manifest in functional migration readouts and highlight why migration or invasion outcomes should not be interpreted as standalone evidence of a discrete EMT state. We highlight that migration patterns observed in scratch (wound healing) or transwell assays do not always reflect complete EMT activation, as hybrid cells may exhibit enhanced migratory capacity, including collective migration, compared with fully mesenchymal phenotypes. This necessitates a more integrated approach that combines molecular profiling with functional outcomes to avoid over interpretation of laboratory data. By refining the understanding of metastatic mechanisms, this work aligns with the United Nations’ Sustainable Development Goal (SDG) 3 (Good Health and Well-being), specifically contributing to the reduction of premature mortality from non-communicable diseases through improved oncological insights. Such precision in interpreting EMT states is crucial for identifying targetable vulnerabilities and advancing personalized therapeutic strategies in aggressive breast cancer.
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BibTeX
@article{utami2026unraveling,
title = {{Unraveling the EMT Spectrum in Aggressive Breast Cancer: Bridging Molecular Hybrid States with Functional Assay Interpretation}},
author = {Nurul Utami and Karina Fitria Alhaq and Nandina Oktavia and Muhammad Hasan Bashari and Hermin Aminah Usman and Astrid Feinisa Khairani},
journal = {OncoTargets and Therapy},
year = {2026},
month = oct,
doi = {10.2147/ott.s640642},
url = {https://doi.org/10.2147/ott.s640642},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Unraveling the EMT Spectrum in Aggressive Breast Cancer: Bridging Molecular Hybrid States with Functional Assay Interpretation
AU - Nurul Utami
AU - Karina Fitria Alhaq
AU - Nandina Oktavia
AU - Muhammad Hasan Bashari
AU - Hermin Aminah Usman
AU - Astrid Feinisa Khairani
PY - 2026
DA - 2026/10/27
JO - OncoTargets and Therapy
DO - 10.2147/ott.s640642
UR - https://doi.org/10.2147/ott.s640642
AB - Recent evidence redefines the Epithelial-Mesenchymal Transition (EMT) from a rigid binary switch into a fluid, multidimensional spectrum. In aggressive breast cancer subtypes, particularly Triple-Negative Breast Cancer (TNBC), this plasticity gives rise to hybrid phenotypes that paradoxically co-express epithelial and mesenchymal traits. These intermediate states fuel collective cell migration and therapeutic evasion by maintaining a balance between cellular adhesion and motility. This review synthesizes current molecular insights into EMT plasticity, focusing on the interconnected regulatory networks involving core transcription factors such as SNAIL, ZEB1/2, and TWIST, alongside upstream signaling pathways like TGF-β and Wnt/β-catenin. Beyond summarizing EMT plasticity and hybrid states, this review specifically bridges the molecular EMT spectrum with the interpretation of common functional migration and invasion assays. We critically evaluate how these molecular states may manifest in functional migration readouts and highlight why migration or invasion outcomes should not be interpreted as standalone evidence of a discrete EMT state. We highlight that migration patterns observed in scratch (wound healing) or transwell assays do not always reflect complete EMT activation, as hybrid cells may exhibit enhanced migratory capacity, including collective migration, compared with fully mesenchymal phenotypes. This necessitates a more integrated approach that combines molecular profiling with functional outcomes to avoid over interpretation of laboratory data. By refining the understanding of metastatic mechanisms, this work aligns with the United Nations’ Sustainable Development Goal (SDG) 3 (Good Health and Well-being), specifically contributing to the reduction of premature mortality from non-communicable diseases through improved oncological insights. Such precision in interpreting EMT states is crucial for identifying targetable vulnerabilities and advancing personalized therapeutic strategies in aggressive breast cancer.
SN - 1178-6930
ER -