Tumor-promoting functions of transforming growth factor-β in progression of cancer

Abstract

Transforming growth factor-β (TGF-β) elicits both tumor-suppressive and tumor-promoting functions during cancer progression. Here, we describe the tumor-promoting functions of TGF-β and how these functions play a role in cancer progression. Normal epithelial cells undergo epithelial-mesenchymal transition (EMT) through the action of TGF-β, while treatment with TGF-β and fibroblast growth factor (FGF)-2 results in transdifferentiation into activated fibroblastic cells that are highly migratory, thereby facilitating cancer invasion and metastasis. TGF-β also induces EMT in tumor cells, which can be regulated by oncogenic and anti-oncogenic signals. In addition to EMT promotion, invasion and metastasis of cancer are facilitated by TGF-β through other mechanisms, such as regulation of cell survival, angiogenesis, and vascular integrity, and interaction with the tumor microenvironment. TGF-β also plays a critical role in regulating the cancer-initiating properties of certain types of cells, including glioma-initiating cells. These findings thus may be useful for establishing treatment strategies for advanced cancer by inhibiting TGF-β signaling.

Key words::

• Angiogenesis
• cancer-initiating cell
• EMT
• invasion
• metastasis
• TGF-β

Acknowledgements

This work was supported by KAKENHI (grants-in-aid for scientific research on Innovative Area (Integrative Research on Cancer Microenvironment Network; grant number 22112002)) and for Young Scientists (B) (grant numbers 22700876 (S.E.) and 22790750 (D.K.)); the Global Center of Excellence Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; a Grant-in-Aid for Cancer Research for the Third-Term Comprehensive 10-Year Strategy for Cancer Control (H22-013) from the Ministry of Health, Labour and Welfare of Japan; and a grant from Swedish Cancer Society (grant number 10 0452).

Declaration of interest: K.M. is supported by a research fund from Antisense Pharma GmbH (Germany). The authors alone are responsible for the content and writing of the paper.