a mini review on the multifaceted role of tgf-β in metastasis progression: molecular mechanisms and novel therapeutic strategies

Tgf-β acts as a cytokine with a dual role in tumor control and metastasis. in the early stages, tgf-β functions as a tumor suppressor, helping to maintain cellular homeostasis. however, as cancer progresses, this cytokine can promote tumor invasion and metastasis by regulating the tumor microenvironment and the immune system. tgf-β controls multiple functions, including growth regulation, differentiation, apoptosis, and cell signaling, through smad and non-smad signaling pathways. in cancer, the signaling pathway of this cytokine activates the epithelial-mesenchymal transition (emt) process, leading to reduced cell adhesion, increased motility, and ultimately, tumor invasion. these changes are also associated with resistance to chemotherapy. additionally, tgf-β stimulates angiogenesis by inducing pro-angiogenic factors such as vegf and pdgf, which are crucial for the spread of metastatic tumors. furthermore, this cytokine plays a significant role in tumor immune evasion by suppressing the activity of t cells and nk cells while promoting regulatory t cells (tregs). targeted therapies against tgf-β, including ligand receptors, monoclonal antibodies, kinase inhibitors, and antisense oligonucleotides (aso), have shown promising results in preclinical and clinical studies. however, challenges such as tumor resistance to therapy and side effects due to the broad inhibition of tgf-β isoforms remain. therefore, efforts to improve tgf-β-based therapies and combine them with other treatments, including immunotherapy, are ongoing.