The role of TGF-β1 and VEGF-A in breast cancer progression

Transforming Growth Factor Beta (TGF-β) and Vascular Endothelial Growth Factor A (VEGF-A) have important and complex roles in breast cancer progression. In early-stage breast cancer, TGF-β functions as a tumor suppressor by inhibiting cell proliferation through cell cycle arrest and induction of apoptosis. However, in advanced stages, TGF-β switches roles to become a tumor promoter by facilitating epithelial to mesenchymal transition (EMT), which enhances cancer cell migration, invasion, and metastasis. In addition, TGF-β modulates the tumor microenvironment to suppress antitumor immune responses and stimulates angiogenesis through increased expression of VEGF-A and other pro-angiogenic factors. VEGF-A, on the other hand, is a key driver of angiogenesis, the formation of new blood vessels that provide oxygen and nutrients for tumor growth. VEGF-A expression is enhanced by hypoxic conditions through the activation of hypoxia-inducible factor 1-alpha (HIF-1α). The interaction between TGF-β and VEGF-A shows significant synergy in promoting endothelial cell proliferation and migration as well as modulation of the tumor microenvironment to support angiogenesis and metastasis. This study highlights the importance of understanding the interaction between TGF-β and VEGF-A to identify biomarkers that relevant for patient stratification as well as the development of innovative therapeutic targets for breast cancer treatment.