TGF-β at the crossroads of multiple prognosis in breast cancer, and beyond

Transforming growth factor β (TGF-β), a pluripotent cytokine and a multifunctional growth factor has a crucial role in varied biological mechanisms like invasion, migration, epithelial-mesenchymal transition, apoptosis, wound healing, and immunosuppression. Moreover, it also has an imperative role both in normal mammary gland development as well as breast carcinogenesis. TGF-β has shown to have a paradoxical role in breast carcinogenesis, by transitioning from a growth inhibitor to a growth promoter with the disease advancement. The inter-communication and crosstalk of TGF-β with different signaling pathways has strengthened the likelihood to explore it as a comprehensive biomarker. In the last two decades, TGF-β has been studied extensively and has been found to be a promising biomarker for early detection, disease monitoring, treatment selection, and tumor progression making it beneficial for disease management. In this review, we focus on the signaling pathways and biological activities of the TGF-β family in breast cancer pathogenesis and its role as a circulatory and independent biomarker for breast cancer progression and metastasis. Moreover, this review highlights TGF-β as a drug target, and the underlying mechanisms through which it is involved in tumorigenesis that will aid in the development of varied therapies targeting the different stages of breast cancer.