Introduction: Compared to other growth factors, cell type, and environment, almost all TGF-b family proteins promote cell growth and proliferation. Beta growth factor (TGF-b) is a multifunctional polypeptide and its roles include controlling a significant number of cellular mechanisms and biological metabolisms. For an overview of the signaling pathway, TGF-b molecules bind to membrane receptors that have Ser / Thr kinase activity and are then transported into the cell by nonSMAD / SMAD proteins and then activated by transcription factors in the nucleus. They cause the expression of the target gene. This pathway plays an inhibitory role in the early stages of tumorigenesis with cytostasis and apoptosis, but as cancer cell survival continues, the expression of TGF-b by cancer cells is out of control and increases growth rate, angiogenesis, and metastasis.
Methods: To obtain specialized information and data extraction by entering selected keywords in search engines google scholar, Pubmed, science direct, and NCBI, search and apply filters including full text, abstract and view articles and research documents And we reviewed such as clinical trials, experiments, meta-analyses, systematic reviews, narratives, and case reports, and on the other hand, our priority was on the period 2010 to 2020.
Results: finally, our findings from these researches were that TGF-b signaling controls a very wide and diverse set of cellular processes such as proliferation, detection, differentiation, and adaptation in different species. several factors such as PH, ROS. are effective in activating it. SMADs are a large family of TGF-b signaling pathways that play a large role in this pathway. cooperation between the SMAD and non-SMAD pathways determines the result of the cellular response to TGF-b. the interaction between SMAD and other signaling proteins controls the expression of the target gene at different levels. this paper emphasizes the mechanism of TGF-b signaling along the SMAD and non-SMAD pathways and the importance of mutations in functional components of the TGF-b family. although sometimes mutations in these proteins may occur and disrupt the TGF-b signaling pathway, eventually leading to a variety of cancers.
Conclusion: the purpose of this paper was to investigate the TGF-b pathway in the SMAD and non-SMAD branches. SMAD proteins are expressed everywhere and in all adult tissues of the body. in this article, we discussed the types of SMAD proteins and their functions, which included R-SMAD, CO-SMAD, and I-SMAD. R-SMAD included SMAD1, SMAD2, SMAD3, SMAD5, and SMAD8 which sometimes use SMAD9 instead of SMAD8, CO-SMAD contained only SMAD4, and I-SMAD is divided into two subgroups SMAD6 and SMAD7. among the type of SMADs, only R-SMADs are phosphorylated and activated directly by type 1 kinases. non-SMAD paths are several conditions such as the presence of type 2, TGF-b receptors in the lipid complex. mutations in the TGF-b pathway lead to a variety of spectra of SMAD2 and SMAD3 were high similar to the mutation spectrum of SMAD4 both in mutation type and location.