Title:Positive and Negative Effects of TGF-β Signaling Pathways in Carcinogenesis
VOLUME: 12 ISSUE: 2
Author(s):Irfan Ullah* and Liling Tang
Affiliation:Key Laboratory of Bio Rheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University, Chongqing 400044, Key Laboratory of Bio Rheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University, Chongqing 400044
Keywords:Transforming growth factor beta, apoptosis, hemostasis, cancers, nucleus, carcinogenesis.
Abstract:Background: Transforming growth factor beta (TGF-β) is a multifunctional protein that
acts as a regulator of cellular function such as proliferation, migration, differentiation, apoptosis,
vascular hemostasis, and development of organisms. As the TGF-β is the key player of cell proliferation
and apoptosis it also involves in different diseases such as autoimmune disorder and vascular
disease. The TGF-β signaling pathway starts with the activation of TGFBRII and TGFBRI that
trigger the phosphorylation of Smad cascade. The Smads complexes (Smad4+R-Smad) translocate
to the nucleus and induce the transcription of the target gene. The dysregulation of the TGF-β signaling
pathways has been reported in many human diseases including cancer. TGF-β acts as a tumor
suppressor in the early stage of cancer but in late-stage show oncogenic factor and loss antiproliferative
response.
Objective: This reviews article determines the mechanism of TGF-β signaling pathways, the effect
of TGF-β component on different cancers and provides a brief overview how it (TGF-β) acts as a
tumor suppressor and promoter.
Conclusion:TGF-β signaling pathways have a multifaceted and fundamental role in human development.
It acts as a double-edged sword, both tumor suppressor, and tumor promoter. The tumor
suppressor role is commonly designated as antiproliferative and apoptotic effects. TGF-β stops cell
cycle at the G1 phase and promotes apoptosis. However, in advance stage of the tumor, it lost suppressor
activities and begin tumor promotor due to the mutation in some component of the TGF-β
pathway. Thus, The TGF-β can no longer control the cell cycle and proliferate the cancer cell. The
increased production of TGF-β induces tumor invasion, motility, metastasis, immunosuppression
epithelial-to-mesenchymal transition and angiogenesis. To study the exact molecular mechanism of
TGF-β in the cancer cell and determine the oncogenic activities can provide successful and new
therapeutic approach to reestablish the ordinary function of TGF-β.
