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Open AccessArticle
Heterogeneous Evolution of Breast Cancer Cells—An Endogenous Molecular-Cellular Network Study
by
Tianqi Li
Tianqi Li 1,
Yong-Cong Chen
Yong-Cong Chen 1,* and
Ping Ao
Ping Ao 2
1
Center for Quantitative Life Sciences & Physics Department, Shanghai University, Shanghai 200444, China
2
School of Biomedical Engineering, Sichuan University, Chengdu 610065, China
*
Author to whom correspondence should be addressed.
Submission received: 2 July 2024
/
Revised: 23 July 2024
/
Accepted: 25 July 2024
/
Published: 26 July 2024
Simple Summary
The classification of breast cancer has been a complex subject, with diverse origins of normal breast epithelial cells and evolutionary pathways contributing to its extensive heterogeneity, which further complicates the treatment process. We developed a dynamic network model to simulate the emergence of different cellular states and explore the underlying biological mechanisms. This model revealed cellular states that align with four recognized molecular subtypes of breast cancer. It also identified feedback loops that either reinforce or facilitate phenotypic transitions, and allowed us to trace these transitions through the model’s topological structure. This approach provides new insights into the mechanisms driving breast cancer heterogeneity and may benefit the development of more targeted therapeutic strategies.
Abstract
Breast cancer heterogeneity presents a significant challenge in clinical therapy, such as over-treatment and drug resistance. These challenges are largely due to its obscure normal epithelial origins, evolutionary stability, and transitions on the cancer subtypes. This study aims to elucidate the cellular emergence and maintenance of heterogeneous breast cancer via quantitative bio-process modeling, with potential benefit to therapeutic strategies for the disease. An endogenous molecular–cellular hypothesis posits that both pathological and physiological states are phenotypes evolved from and shaped by interactions among a number of conserved modules and cellular factors within a biological network. We hereby developed a model of core endogenous network for breast cancer in accordance with the theory, quantifying its intrinsic dynamic properties with dynamic modeling. The model spontaneously generates cell states that align with molecular classifications at both the molecular and modular level, replicating four widely recognized molecular subtypes of the cancer and validating against data extracted from the TCGA database. Further analysis shows that topologically, a singular progression gateway from normal breast cells to cancerous states is identified as the Luminal A-type breast cancer. Activated positive feedback loops are found to stabilize cellular states, while negative feedback loops facilitate state transitions. Overall, more routes are revealed on the cellular transition between stable states, and a traceable count explains the origin of breast cancer heterogeneity. Ultimately, the research intended to strength the search for therapeutic targets.
Share and Cite
MDPI and ACS Style
Li, T.; Chen, Y.-C.; Ao, P.
Heterogeneous Evolution of Breast Cancer Cells—An Endogenous Molecular-Cellular Network Study. Biology 2024, 13, 564.
https://doi.org/10.3390/biology13080564
AMA Style
Li T, Chen Y-C, Ao P.
Heterogeneous Evolution of Breast Cancer Cells—An Endogenous Molecular-Cellular Network Study. Biology. 2024; 13(8):564.
https://doi.org/10.3390/biology13080564
Chicago/Turabian Style
Li, Tianqi, Yong-Cong Chen, and Ping Ao.
2024. "Heterogeneous Evolution of Breast Cancer Cells—An Endogenous Molecular-Cellular Network Study" Biology 13, no. 8: 564.
https://doi.org/10.3390/biology13080564
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