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Updated: Sep 27, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGF-β induced reprogramming and drug resistance in triple-negative breast cells
1Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China. wuguoyu@gdpu.edu.cn.
Background:
The development of drug resistance remains to be a major cause of therapeutic failure in breast cancer patients. How drug-sensitive cells first evade drug inhibition to proliferate remains to be fully investigated.
Methods:
Here we characterized the early transcriptional evolution in response to TGF-β in the human triple-negative breast cells through bioinformatical analysis using a published RNA-seq dataset, for which MCF10A cells were treated with 5 ng/ml TGF-β1 for 0 h, 24 h, 48 h and 72 h, and the RNA-seq were performed in biological duplicates. The protein-protein interaction networks of the differentially expressed genes were constructed. KEGG enrichment analysis, cis-regulatory sequence analysis and Kaplan-Meier analysis were also performed to analyze the cellular reprograming induced by TGF-β and its contribution to the survival probability decline of breast cancer patients.
Result:
Transcriptomic analysis revealed that cell growth was severely suppressed by TGF-β in the first 24 h but this anti-proliferate impact attenuated between 48 h and 72 h. The oncogenic actions of TGF-β happened within the same time frame with its anti-proliferative effects. In addition, sustained high expression of several drug resistance markers was observed after TGF-β treatment. We also identified 17 TGF-β induced genes that were highly correlated with the survival probability decline of breast cancer patients.
Conclusion:
Together, TGF-β plays an important role in tumorigenesis and the development of drug resistance, which implies potential therapeutic strategies targeting the early-stage TGF-β signaling activities.
Insights
Transforming growth factor-beta (TGF-β) initially suppresses breast cancer cell growth but later promotes drug resistance and tumor progression. Targeting early TGF-β signaling may offer new therapeutic strategies for breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Drug resistance is a primary cause of therapeutic failure in breast cancer.
- Understanding early cellular responses to therapeutic agents is crucial for overcoming resistance.
Purpose of the Study:
- To investigate the early transcriptional changes in response to TGF-β in triple-negative breast cancer cells.
- To identify genes and pathways involved in TGF-β-induced cellular reprogramming and drug resistance.
Main Methods:
- Bioinformatic analysis of RNA-sequencing data from MCF10A cells treated with TGF-β1.
- Construction of protein-protein interaction networks.
- KEGG enrichment, cis-regulatory sequence, and Kaplan-Meier analyses were performed.
Main Results:
- TGF-β initially suppressed cell growth within 24 hours, with effects diminishing by 48-72 hours.
- TGF-β exhibited oncogenic actions concurrently with its anti-proliferative effects.
- Sustained high expression of drug resistance markers and 17 TGF-β-induced genes correlated with decreased patient survival.
Conclusions:
- TGF-β plays a significant role in breast cancer tumorigenesis and the development of drug resistance.
- Early-stage TGF-β signaling modulation presents a potential therapeutic avenue.
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