Biphasic Role of TGF-β in Cancer Progression: From Tumor Suppressor to Tumor Promotor

Transforming growth factor-β (TGF-β) can elicit a biphasic effect on tumor progression by inhibiting cell proliferation and promoting apoptosis at early phases and promoting migration, epithelial to mesenchymal transition and invasion at late phases. Here, we review how TGF-β signaling pathways mediate potent cytostatic effects in normal and premalignant cells and how tumor cells become selectively resistant to these effects. In addition, we discuss how alterations in TGF-β signaling switch its behavior from tumor suppressor into tumor promoter. TGF-β not only acts directly on tumor cells but also facilitates a favorable microenvironment for rapid tumor growth and metastasis. Finally, we provide an overview of the opportunities and challenges for the therapeutic targeting of TGF-β-induced pro-oncogenic responses.