TGF-β: An Important Mediator of Allergic Disease and a Molecule with Dual Activity in Cancer Development

Abstract

The transforming growth factor-β (TGF-β) superfamily is a family of structurally related proteins that includes TGF-β, activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF-β superfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF-β is involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF-β receptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF-β with various pathological entities such as allergic diseases and cancer, yielding a new area of research known as “allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF-β is involved. Here, we review recent studies that suggest an important role for TGF-β in both allergic disease and cancer progression.

Relaxin-2 Does Not Ameliorate Nephropathy in an Experimental Model of Type-1 Diabetes

“…bodyweight in Table 1), and this may have impacted on the activation of latent TGF-β. We hypothesize as follows: Plasmin and thrombospondin are the main TGF activators [46]. The activation of plasmin, in turn, is decreased in cachexia states owing to the up-regulation of plasminogen activator inhibitor [47].…”

Adenovirus-mediated P311 inhibits TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells <i>via</i> TGF-β1-Smad-ILK pathway

“…The Smad family has 8 members forming three subfamilies: the R-Smads (receptor regulated Smads), the Co-Smads (common Smad mediators), and the I-Smads (inhibitory Smads), which are the main TGF-β signaling transducers, mediating signaling from cell surface receptors to nuclear target genes (24). Homologous proteins Smad2 and Smad3 belong to the R-Smads, which are highly activated in the fibrotic kidney.…”

TGF-ß alterations in oral squamous cell carcinoma. Narrative review

“…Smad proteins are responsible for continuing the signaling cascade caused by TGF-ß from the cytoplasm to the target genes located in the nucleus. Smad proteins possess a highly conserved terminal portion consisting of a C-terminal (MH1) and N-terminal (MH2) 18 connected by a proline-rich region 12 .…”

“…Once TßR-I is activated, phosphorylation of the complex formed by SMAD2 and SMAD3 occurs 19 . This results in the release of SARA proteins, allowing the binding of R-Smad to SMAD4, facilitating their translocation into the nucleus of the cell 12 .…”