TGF beta Signaling Pathway

Transforming growth factor β (TGF beta) is a multi-functional secreted cytokine that plays pivotal roles in embryonic development and adult tissue maintenance ⁽¹⁾, moreover it regulates numerous biological processes including promotion of cell differentiation and proliferation, control of cell apoptosis and cell cycle, regulation of the epithelial–mesenchymal transition (EMT), angiogenesis, extracellular matrix (ECM) formation, suppression of immune response, and maintenance of genomic stability and stem cell homeostasis ⁽²⁾, (in blue among AnyGenes pathways).

It has been proved that TGFβ plays dual roles in tumor progression as tumor-promoter or suppressor. In an early stage, TGFβ inhibits cell proliferation and is involved in cell apoptosis. In an advanced tumor, TGFβ signaling pathway induces tumor invasion and metastasis through promoting angiogenesis, epithelial–mesenchymal transition, and immune escape ⁽³⁾.

Abnormal TGFβ signaling pathway cause congenital defects, fibrotic diseases, immune dysregulation ⁽⁴⁾, craniofacial cleft palate syndrome, and the autosomal dominant abnormality of the Rendu–Osler–Weber syndrome; cardiovascular pathologies including atherosclerosis, hypertension and rare abnormalities of the vasculature such as aneurysms; connective tissue and bone diseases like the Marfan syndrome and osteoporosis; muscular and reproductive disorders; certain hereditary cancer syndromes and many sporadic malignancies such as brain, breast, colon, liver, lung, prostate, haematopoetic malignancies and Cholangiocarcinoma ^(1,5,6,8).
TGFβ pathway contributes to generate a favorable microenvironment for tumor growth and metastasis throughout all the steps of carcinogenesis ⁽⁷⁾.
Recent studies have revealed roles of TGFβ pathway in tumor immune evasion and poor responses to cancer immunotherapy ⁽⁴⁾.
Targeting the TGFβ pathway for cancer therapy may be considered primarily as a microenvironment-targeted strategy ⁽⁷⁾.