Related Experiment Video
Updated: Jun 1, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
The complexities of TGF-β action during mammary and squamous cell carcinogenesis
Erin C Connolly1, Rosemary J Akhurst
1Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, California 94143-0512, USA.
Abstract:
Many advanced tumors produce excess amounts of Transforming Growth Factor-β (TGF-β), which is a potent growth inhibitor of normal epithelial cells. However, in tumors its homeostatic action on cells can be diverted along several alternative pathways. Thus, TGF-β signaling has been reported to elicit a preventative or tumor suppressive effect during the earlier stages of tumorigenesis, but later in tumor development, when carcinoma cells become refractory to TGF-β-mediated growth inhibition, response to TGF-β signaling elicits predominantly tumor progressing effects. This is not a simple switch from suppression to progression, but more like a rheostat, involving multiple complementary and antagonizing activities that slowly tip the balance from one to the other. This review will focus on the multiple activities of TGF-β in regulation of two epithelial tumor types, namely squamous cell carcinoma and breast cancer. Basic findings in current mouse models of cancer are presented, as well as a discussion of the complicating issue of outcome of altered TGFβ signaling depending on genetic variability between mouse strains. This review also discusses the role TGF-β within the tumor microenvironment particularly its ability to polarize the microenvironment towards a pro-tumorigenic milieu.
Insights
Transforming Growth Factor-β (TGF-β) initially suppresses tumors but later promotes their progression. Its dual role, like a rheostat, is crucial in squamous cell carcinoma and breast cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Advanced tumors often overproduce Transforming Growth Factor-β (TGF-β), a molecule with complex roles in cancer.
- TGF-β acts as a growth inhibitor for normal epithelial cells, but its function is altered in tumor cells.
Purpose of the Study:
- To review the multifaceted roles of TGF-β signaling in the progression of squamous cell carcinoma and breast cancer.
- To explore how TGF-β's effects shift from tumor suppression to tumor promotion during tumorigenesis.
Main Methods:
- Review of current findings from mouse models of cancer.
- Analysis of the impact of genetic variability on TGF-β signaling outcomes.
- Discussion of TGF-β's role in shaping the tumor microenvironment.
Main Results:
- TGF-β exhibits a dual role, suppressing tumors in early stages and promoting progression in later stages.
- This shift is not abrupt but gradual, influenced by multiple interacting cellular activities.
- TGF-β contributes to a pro-tumorigenic tumor microenvironment.
Conclusions:
- TGF-β signaling is a critical regulator in epithelial cancers like squamous cell carcinoma and breast cancer.
- Understanding the context-dependent, rheostat-like activity of TGF-β is vital for cancer therapy.
- The tumor microenvironment is significantly influenced by TGF-β, promoting cancer progression.
Related Concept Videos
01:16TGF - β Signaling Pathway
02:17The Tumor Microenvironment
02:38Mitogens and the Cell Cycle