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When TGF-β signaling fails to control NF-κB activity in cancer cells, this has at least two potential effects: first, it enables the malignant tumor to persist in the presence of activated immune cells, and second, the cancer cell outlasts immune cells because it survives in the presence of apoptotic, and anti-inflammatory mediators.
Transforming growth factor ([attribution needed], or TGF) is used to describe two classes of polypeptide growth factors, TGFα and TGFβ. The name "Transforming Growth Factor" is somewhat arbitrary, since the two classes of TGFs are not structurally or genetically related to one another, and they act through different receptor mechanisms .
Defects in Smad signaling can result in TGF-B resistance, causing dysregulation of cell growth. Deregulation of TGF-B signaling has been implicated in many cancer types, including pancreatic, colon, breast, lung, and prostate cancer. [36] Smad4 is most commonly mutated in human cancers, particularly pancreatic and colon cancer.
It acts as a mediator of the signals initiated by the transforming growth factor beta (TGF-β) superfamily of cytokines, which regulate cell proliferation, differentiation and death. [7] [8] Based on its essential role in TGF beta signaling pathway, SMAD3 has been related with tumor growth in cancer development.
Transforming growth factor beta (TGF-β) is a potent cell regulatory polypeptide homodimer of 25kD. [1] It is a multifunctional signaling molecule with more than 40 related family members. TGF-β plays a role in a wide array of cellular processes including early embryonic development, cell growth, differentiation, motility, and apoptosis. [2]
The TGF beta signaling pathway is involved in a wide range of cellular process and subsequently is very heavily regulated. There are a variety of mechanisms where the pathway is modulated either positively or negatively, including the agonists for ligands and R-SMADs, the decoy receptors, and the ubiquitination of R-SMADs and receptors.
Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene. [5] [6]
SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction.