Crosstalk between p38 and Smad3 through TGF-β1 in JEG-3 choriocarcinoma cells

Abstract

Abstract. Choriocarcinoma is a highly malignant trophoblastic tumor related to pregnancy that often occurs with a complete hydatidiform mole. It grows quickly and can also widely metastasize to other organs or tissues through both the venous and lymphatic systems. The transforming growth factor-β1 (TGF-β1) belongs to a growth factor superfamily and has been suggested to play a critical role in regulating the genesis and development of choriocarcinoma through a variety of Smad-independent pathways, including the p38 MAPK pathway. Previous studies indicated that TGF-β can activate the p38 MAPK pathway. In this study, we investigated Smad and p38 MAPK signaling in JEG-3 choriocarcinoma cells using p38 MAPK inhibitor and TGF-β receptor inhibitor. Immunofluorescence and western blot assays were used to detect the proteins in Smad and p38 MAPK pathways. Our data demonstrated that TGF-β can activate Smad3 and induce Smad3 translocation into the nucleus in JEG-3 cells. Blockade of the TGF-β pathway significantly reduced the expression levels of p38 and phospho-p38. p38 MAPK inhibitors (SB 203580) can attenuate TGF-β1-induced Smad3 expression and suppress the activation of smad3. These findings indicate crosstalk between p38 and smad3 through TGF-β1 in choriocarcinoma cells.

MicroRNA-891b is an independent prognostic factor of pancreatic cancer by targeting Cbl-b to suppress the growth of pancreatic cancer cells

“…In addition, we found that miR-891b overexpression or Cbl-b knockdown increased the expression of Smad3 protein. In choriocarcinoma cells, the expression of Smad3 could be promoted by TGF-β1, and suppressed by p38 MAPK inhibitor [29]. In the present study, Smad3 mRNA level was increased by miR-891b overexpression or Cbl-b knockdown.…”

Crosstalk between the p38 and TGF-β signaling pathways through TβRI, TβRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells

“…Following this, 5 ng/ml TGF-β1 was added into each well, except those of the control group, and incubation was continued for 2 h. Previous results from our laboratory indicated that p38 MAPK inhibitors can attenuate TGF-β1-induced Smad3 protein expression (21); thus; we further examined the effect of p38 inhibitors on the transcriptional levels of Smad3 in response to TGF-β1. Compared with the control group, the mRNA expression levels of Smad3 were significantly elevated in TGF-β1 group (P<0.05) (Fig.…”

“…Our previous study demonstrated that blocking the TGF-β pathway by using a TGF-β receptor inhibitor significantly reduces the expression levels of p38 and phospho-p38 in JEG-3 cells. Additionally, treatment of JEG-3 cells with a p38 MAPK inhibitor (SB 203580) attenuated TGF-β1-induced Smad3 protein expression and suppressed the activation of Smad3 (21). These results suggested that there is crosstalk between p38 MAPK and Smad3 through TGF-β signaling in human choriocarcinoma.…”

Profiling of serum metabolites in advanced colon cancer using liquid chromatography‑mass spectrometry

“…A previous study reported that vitamin D and its derivatives can induce the expression of bone morphogenetic protein (BMP) and activate the BMP-Smad signaling pathway (39). The BMP-Smad signaling pathway is involved in the pathway for enzyme-coupled receptor signal transduction, and BMP is one β-tumor necrosis factor (38,40) that regulates cell proliferation, differentiation and apoptosis. Furthermore, previous in vitro experiments demonstrated that vitamin D and its metabolites or analogs induce BMP overexpression and activates BMP-Smad signaling pathway to suppress the development of colon cancer (41,42).…”