Mechanistically, calcitriol suppressed EMT through different signaling pathways: (1) calcitriol suppressed Smad2/3 phosphorylation through reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-β1-stimulated RCC cells; (2) calcitriol inhibited STAT3 activation in LPS-stimulated RCC cells; (3) calcitriol inhibited β-catenin/TCF-4 activation through promoting integration of VDR with β-catenin in TGF-β1-unstimulated RCC cells.
LEF1/integrin αMβ2 expression was regulated by TGF-β1, and LEF1/integrin αMβ2 was involved in TGF-β1's improvement effects on the proliferation and metastasis of RCC.
Mechanism analysis revealed that ERβ can promote RCC cell invasion via an increase in transforming growth factor β1 (TGF-β1)/SMAD3 signals, and interrupting TGF-β1/SMAD3 signals with a TGFβR1 inhibitor can reverse/block ERβ-increased RCC cell migration.
Subsequently, upregulating protein level of TGF-β1 with the overexpression of CD82 could rescue the malignant behaviors inhibited by CD82 which indicated that CD82 played its inhibitory role in RCC partially by attenuating the expression of TGF-β1.
We hypothesized that 1) changes in the expression of adhesion related genes may influence survival rate of patients with renal cell carcinoma and 2) TGF-β1 may contribute to changed expression of adhesion related genes.
To investigate the effect of transforming growth factor-β1 (TGF-β1) on the expression of Fascin1 protein and its impact on cell invasion and metastasis in human renal carcinoma.
Furthermore, Western blot analysis was conducted to identify the influence of BX357664 on epithelial-to-mesenchymal transition, matrix metalloproteinase 2, matrix metalloproteinase 9, and transforming growth factor-beta 1 (TGF-β1)/p38/HSP27 signaling pathway in RCC.
These data suggest that MMP-13 expression is elevated in RBM relative to primary RCC and adjacent normal kidney, and is regulated at the cellular level by TGF-beta1.
To further assess the role of BIGH3 in RCC, we investigated the mRNA expression levels of BIGH3, TGFbeta1, PAI-1 and also of TGF-beta1 related genes in 53 RCC and 30 normal kidney tissues by quantitative real-time RT-PCR (QRT-PCR).