A Mini Review on the Multifaceted Role of TGF-β in Metastasis Progression: Molecular Mechanisms and Novel Therapeutic Strategie

Abstract

Transforming growth factor-beta (TGF-β) plays a dual role in tumor regulation andmetastasis. In the early stages of cancer, TGF-β functions as a tumor suppressor,maintaining cellular homeostasis. However, as cancer progresses, this cytokine canpromote tumor invasion and metastasis by modulating the tumor microenvironment andimmune responses. TGF-β regulates multiple cellular functions, including growth control,differentiation, apoptosis, and signaling, through SMAD and non-SMAD pathways. Incancer, TGF-β signaling activates the epithelial-mesenchymal transition (EMT), leadingto decreased cell adhesion, increased motility, and enhanced tumor invasiveness. Thesealterations are also linked to chemotherapy resistance. Additionally, TGF-β stimulatesangiogenesis by inducing pro-angiogenic factors such as vascular endothelial growthfactor (VEGF) and platelet-derived growth factor (PDGF), both of which are essential formetastatic tumor expansion. Furthermore, TGF-β contributes to tumor immune evasionby suppressing T-cell and natural killer (NK) cell activity while promoting regulatory Tcells (Tregs). Targeted therapies against TGF-β—including ligand receptor inhibitors,monoclonal antibodies, kinase inhibitors, and antisense oligonucleotides (ASO)—haveshown promise in preclinical and clinical studies. However, challenges such as tumorresistance and adverse effects resulting from broad TGF-β inhibition remain. Therefore,ongoing research aims to refine TGF-β-based therapies and integrate them with othertreatment modalities, including immunotherapy