Targeting TGF-β signal transduction for fibrosis and cancer therapy

Abstract

Transforming growth factor β (TGF-β) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, and adult homeostasis. The role of TGF-β in fibrosis and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, overexpressed TGF-β causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, and cancer. Given the critical role of TGF-β and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-β signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-β therapeutics has lagged. In this review, we summarized the biological process of TGF-β, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-β-targeting therapies.

A bioinformatics analysis: ZFHX4 is associated with metastasis and poor survival in ovarian cancer

“…Coincidentally, Zeb1 and Zeb2 were also two members of zinc finger homobox family, and they shared similar molecular structures with ZFHX4 [ 45 ], which rendered the function of ZFHX4 as an EMT inducer reasonable. Besides, ZFHX4 could be modulated by canonical pathways for EMT regulation, such as TGF-β signaling pathway [ 46 , 47 ], which further supported the contributions of ZFHX4 to EMT. Simultaneously, we found the positive correlation between ZFHX4 and ECM-related genes.…”

Chlorfortunones A and B, Two Sesquiterpenoid Dimers, Possessing Dispiro[4,2,5,2]pentadecane-6,10,14-tren Moiety from Chloranthus fortunei

“…Transforming growth factor-β (TGF-β) is the key regulator of cancer metastasis and fibrosis diseases. 15 As our group′s ongoing research on natural TGF-β inhibitors, 16 − 18 compounds 1 and 2 were tested for in vitro TGF-β inhibitory activity. The results showed that only compound 1 significantly downregulated the TGF-β-induced p-Smad2 expression in a concentration-dependent manner without any impact on the expression of Smad2/3 protein in MDA-MB-231 cells ( Figure 5 A).…”

“…Transforming growth factor-β (TGF-β) is the key regulator of cancer metastasis and fibrosis diseases . As our group′s ongoing research on natural TGF-β inhibitors, − compounds 1 and 2 were tested for in vitro TGF-β inhibitory activity.…”

Pancreatic cancer-associated fibroblasts express tumor-suppressive microRNAs

“…Nevertheless, the two signaling pathways are also intertwined with one another in noncanonical fashion, i.e. TGFβ is also known to be capable of activating signal proteins in the RAS/MAPK or PI3K/AKT pathways 11 . Other CAF-DE-miRNAs, such as miR-136-5p, miR-137-3p, miR-139-5p and miR-139-5p are also actively involved (suppl.…”