The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

Abstract

Intercellular communication is a critical process for all multicellular organisms, and communication among cells is required for proper embryonic development and adult physiology. Members of the Transforming Growth Factor-β β β β (TGF-β β β β) family of secreted proteins communicate information between cells via a complex signaling pathway, and family members are capable of inducing a wide range of cellular responses. The purpose of this review is to provide the reader with a broad introduction to our current understanding of three aspects of the TGF-β β β β family. These are the molecular mechanisms utilized by TGF-β β β β signaling pathways, the developmental roles played by TGF-β β β β family members in a variety of species, and the growing list of cancers in which various TGF-β β β β signaling pathways display tumor suppressor activity.

The nematode parasite Onchocerca volvulus generates the transforming growth factor-beta (TGF-beta)

“…This expression of TGF-β1/LAP in vital adult worms could contribute to the maintenance of physiological integrity of worm tissues as reported for human tissues (Johnson and Newfeld 2002). This is strongly supported by the labeling of large cells of pleomorphic neoplasms in living O. volvulus, suggesting a role for TGF-β in carcinogenesis similar to mammalian cells, where TGF-β can work as tumor promoter and suppressor (Rahimi and Leof 2007).…”

“…The TGF-β signaling pathway is a fundamental and diversified ancient metazoan signal transduction engine, pivotal for animal tissue development, and homeostasis (Johnson and Newfeld 2002;Huminiecki et al 2009). These processes involve cell proliferation, migration, differentiation, and apoptosis, therefore growth, maturation, tissue patterning, organ specification, and physiological integrity regulating tumor formation.…”

Identification of some human genes oppositely regulated during esophageal squamous cell carcinoma formation and human embryonic esophagus development

“…The other genes could not be assigned to certain known pathways. Interestingly, some of the genes that appeared to be involved in the TGF‐beta and WNT pathways are well known for their morphogenetic function 22–25 . A recently proposed hypothesis of morphostatic field and maintaining its molecules called morphostats 26 suggests that maintenance of epithelial tissues requires, like morphogenesis, a method of relating cell position to function.…”

Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-? through Akt inhibition

“…Some studies have provided evidence that the blockade of TGF-b action leads to the suppression of distant metastasis in animal models (Muraoka et al 2002, Yang et al 2002. However, since TGF-b acts as a tumor suppressor, it is still possible that the suppression of TGF-b action itself may promote secondary carcinogenesis (Akhurst 2002;Johnson and Newfeld 2002). Accordingly, it is reasonable to develop a target therapy for the malignant transformationrelated intracellular signaling of TGF-b.…”