Abstract
Transforming growth factor (TGF)-β is a multifunctional cytokine that has important roles in tumor formation, progression, and metastasis. TGF-β is overproduced, and its signaling is deregulated, in a variety of human tumors, including colorectal, gastric, pancreatic, and liver. Therapeutics are being developed to block TGF-β signaling. However, TGF-β also functions as a tumor suppressor in premalignant cells. It is not clear how its function changes from that of a tumor suppressor to a tumor promoter; improvements are needed in our understanding of TGF-β functions in tumor development before we can design inhibitors for use as anticancer therapies. TGF-β regulates not only different tumor-cell autonomous signaling pathways, but also interactions between tumor and host cells, through paracrine mechanisms. We review recent findings about how TGF-β is regulated and its roles in the tumor microenvironment and metastasis, with a focus on gastrointestinal cancers. Improved understanding of TGF-β regulation and how it mediates interaction between cancer epithelial cells, immune cells, and fibroblasts will provide important insights into tumor development and progression.
Original language | English (US) |
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Pages (from-to) | 1167-78 |
Number of pages | 12 |
Journal | Gastroenterology |
Volume | 141 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2011 |
Externally published | Yes |
Keywords
- Animals
- Gastrointestinal Neoplasms
- Humans
- Inflammation Mediators
- Liver Neoplasms
- Neoplasm Invasiveness
- Signal Transduction
- Transforming Growth Factor beta
- Tumor Microenvironment
- Journal Article
- Review