Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma

Ji, Guozhong; Wang, Xuehao; Ma, Lin; Liu, Zheng; Zhang, Ping; Zhang, Faming; Yang, Jian-Bing

doi:10.3748/wjg.v12.i4.644

Cited by 21 publications

(19 citation statements)

References 15 publications

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“…in our previous study, we reported that the expression of Smad4 was lower in Hcc tissue than in adjacent tissues (15). We also validated that the down-regulation of Smad4 in Hcc cells was associated with TGF-β1-induced cell growth inhibition and cellular apoptosis (16).…”

Section: Introductionsupporting

confidence: 74%

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Ji¹

2010

Mol Med Rep

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Abstract. Hepatocellular carcinoma (Hcc) is a highly malignant cancer characterized by rapid progression, easy metastasis and frequent recurrence. Previous studies have shown that the Smad4 signaling pathway plays an important role in the cell growth and apoptosis of Hcc. However, the effect of Smad4 signaling on the invasion and migration of Hcc cells remains unclear. The present study aimed to examine the effects of the transforming growth factor (TGF)-β1-Smad4 signaling pathway on the migration of Hcc cells. lentiviral vectors expressing mirna against Smad4 were constructed to block the expression of Smad4 in Hcc cells, and transwell units were used to investigate the invasive potential of SMMc-7721 cells before and after TGF-β1 treatment. mrna levels of matrix metalloproteinase (MMP)-2 and -9 were analyzed by reverse-transcription Pcr, and concentrations of vascular endothelial growth factor (VeGF), p-JnK, p-p38 and p-erk1/2 proteins were analyzed by Western blotting. The results indicate that TGF-β1 induced cellular invasion in the SMMc-7721 cells. These effects were almost completely blocked by the knockdown of Smad4. reverse-transcription Pcr and Western blot analysis revealed that MMP-2, VeGF, p-JnK and p-p38 were up-regulated by the silencing of Smad4, while the expression of MMP-9 and p-erk1/2 was not affected by Smad4 silencing with or without TGF-β1 stimulation. These findings suggest that TGF-β1-induced SMMc-7721 cell invasion by the up-regulation of MMP-2 and VeGF is Smad4-dependent. The activation of MMP-2 and VeGF may be an important mechanism by which Smad4 is involved in metastasis. TGF-β1-Smad4 signaling may regulate SMMc-7721 cell migration through the activation of the MaPK pathway.

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Section: Introductionsupporting

confidence: 74%

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Ji¹

2010

Mol Med Rep

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“…Smad7 has been demonstrated to inhibit activin signaling and to protect hepatocytes from activin A-induced growth inhibition [145] . Increased expression of Smad7 has been observed in HCC tissue compared to adjacent tissue [146] and in advanced HCC compared to early HCC or dysplastic nodules [147] . No mutations of either Smad 6 or Smad 7 were found in 52 HCC samples [148] .…”

Section: Intracellular Inhibitors Of Signal Transductionmentioning

confidence: 99%

Activins and activin antagonists in hepatocellular carcinoma

Deli

Kreidl²,

Santifaller³

et al. 2008

WJG

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“…Several studies have demonstrated the increased expression of TGF-β1 in various types of cancers and the close association with tumor metastasis, invasion and the poor prognosis of patients (24,25). Although the increased expression of TGF-β1 has been reported to be closely associated with a poor prognosis and tumor angiogenesis in HCC (26)(27)(28), the mechanism concerning the role of the promotion of tumorigenesis remains unclear. The research based on the MDA-MB-231 breast cancer and Ovca420 ovarian cancer cells in vitro revealed that TGF-β1 reduced the expression of TβRIII at the mRNA and protein levels in a dose-and time-dependent manner (29).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of the type III TGF-β receptor enhances metastasis and invasion in hepatocellullar carcinoma progression

Zhang

Sun

et al. 2016

Oncology Reports

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Abstract. The transforming growth factor β (TGF-β) superfamily of cytokines is multifunctional and involved in the regulation of cell growth and differentiation. TGF-β can induce an epithelial-mesenchymal transition (EMT) of both epithelial and endothelial cells. This has consequences for cancer progression in regards to both migration and invasion abilities. The type III TGF-β receptor (TβRIII) is a ubiquitously expressed TGF-β co-receptor which regulates TGF-β signaling and the progression of various types of cancer. Previous studies have shown that TβRIII exhibits abnormal expression and plays an essential role in regulating cancer invasion and metastasis, while little is known in regards to its role in hepatocellular carcinoma (HCC) progression. In the present study, we designed the present research to study the role of TβRIII in the invasion and metastasis of HCC and the possible mechanisms involved. The results demonstrated decreased expression of TβRIII in HCC patient tissues and human HCC cell lines. TGF-β1 stimulation led to the increased migratory ability and reduced expression of TβRIII in HCC cells. In addition, knockdown of TβRIII by small interfering RNA (siRNA) promoted the migration and invasion of HCC cells and induced activation of the Smad2 and Akt pathways. All the results suggest that TβRIII is a novel suppressor of HCC progression.

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Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma

Cited by 21 publications

References 15 publications

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Activins and activin antagonists in hepatocellular carcinoma

Decreased expression of the type III TGF-β receptor enhances metastasis and invasion in hepatocellullar carcinoma progression

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