Role of Transforming Growth Factor-beta in Tumor Invasion and Metastasis

Cancer metastasis is a major determinant of cancer patient mortality. Mounting evidence favors a strong positive role for TGF-beta in human cancer progression. The complex pattern on cross-talk of TGF-beta and the related other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional role of TGF-beta in cancer progression. This review summarizes some of the current understanding of TGF-beta signaling with a major focus in its contribution to the tumor cell invasion and metastasis. Five issues are addressed in this review: (1) TGF-beta signaling, (2) TGF-beta and EMT, (3) TGF-beta and MMP, (4) TGF-beta and Ras, and (5) Role of TGF- 3 in invasion and metastasis. Due to the bifunctional cellular effects of TGF-beta, as a tumor promoter and a tumor suppressor, more precisely defined TGF-beta signaling pathways need to be elucidated. According to the current literature, TGF-beta is clearly a major factor stimulating tumor progression through a complex spectrum of the interplay and cross-talk between various signaling molecules. Understanding the role of TGF-beta in invasion and metastasis will provide valuable information on establishing strategies to manipulate TGF-beta signaling which should be a high priority for the development of anti-metastatic therapeutics.