Regulation of transforming growth factor-β signaling as a therapeutic approach to treating colorectal cancer

Table 2 Roles of individual small mothers against decapentaplegic homolog proteins in the onset and progression of colorectal cancer

Type of SMAD	Role in colorectal cancer	References
SMAD1	Participates in the modification of cell growth, differentiation, apoptosis and other processes that are essential in the regulation of the body’s immune system	[39-42]
	Promotes epithelial-mesenchymal transition process
	By increasing the expression of ATG5 induces autophagy
SMAD2	Inhibits the expression of related functional genes, cell proliferation and regulates the transcriptional response that promotes cell apoptosis	[43,44]
	Expression of SMAD2 is correlated with patient survival
SMAD3	In the formation of a tumor, depending on the stage of the cancer, it plays the double role of an oncogene or a tumor suppressor gene	[45-48]
	Reduces its expression through mir-4429, and inhibits the appearance, development and metastasis of cancer cells
SMAD4	Plays a very important role in the transduction of the TGF-β signaling pathway	[32,49]
	Maintains the cell cycle in the G1 phase, which leads to abnormal tumor proliferation
	Is a tumor suppressor gene
	High mutation rate of SMAD4 in CRC patients was associated with poor prognosis, but not with clinical stage
SMAD5	Mediates TGF-β superfamily ligand signaling pathway and thus influences cancer progression	[50]
	No relevant studies on the role of SMAD5 in CRC patients have been found in the last 5 years
SMAD6	Regulates TGF-β signaling pathway, promotes angiogenesis, stimulates extracellular matrix, and inhibits immunity, thus contributing to tumor growth, diffusion, and metastasis	[51]
	No relevant studies on the role of SMAD6 in CRC patients have been found in the last 5 years
SMAD7	Plays a dual role in different tumor stages, acting as a tumor suppressor gene by inhibiting proliferation and promoting apoptosis in the early stage, and increasing invasion in the late stage, promoting epithelial-mesenchymal transition, which correlates with the degree of malignancy	[52,53]

SMAD: Small mothers against decapentaplegic homolog; ATG5: Autophagy-related gene 5; CRC: Colorectal cancer; TGF: Transforming growth factor.