Dataset Information

Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9.

ABSTRACT: Hepatoma-derived growth factor (HDGF) is commonly over-expressed and plays critical roles in the development and progression in a variety of cancers. It has previously been shown that HDGF is overregulated in prostate cancer cells compared to normal prostate cells, which is correlated with cellular migration and invasion of prostate cancer. Here, the molecular mechanisms of HDGF in prostate cancer is investigated. It is shown that HDGF knockdown reduces prostate cancer cellular migration and invasion in both androgen-sensitive LNCaP cells and androgen-insensitive DU145 and PC3 cells. Furthermore, Western blot analysis reveals that HDGF knockdown inhibits epithelial-mesenchymal transition (EMT) of prostate cancer cells by upregulation of protein E-cadherin and downregulation of proteins N-cadherin, Vimentin, Snail and Slug. In addition, mechanistic studies reveal that proteins MMP2 and MMP9 are down-regulated. In conclusion, our data suggested that HDGF knockdown inhibits cellular migration and invasion in vitro of prostate cancer via modulating epithelial-mesenchymal transition (EMT) signaling pathway, as well as MMP2 and MMP9 signaling pathway. These results supported that HDGF is a relevant protein in the progression of prostate cancer and may serve as a potentially therapeutic target for prostate cancer as well as its downstream targets.

SUBMITTER: Yang F

PROVIDER: S-EPMC5754131 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9.

Yang Feilong F Yu Nengwang N Wang Hui H Zhang Cong C Zhang Zhao Z Li Yanxiang Y Li Dawei D Yan Lei L Liu Hainan H Xu Zhonghua Z

PloS one 20180104 1

Hepatoma-derived growth factor (HDGF) is commonly over-expressed and plays critical roles in the development and progression in a variety of cancers. It has previously been shown that HDGF is overregulated in prostate cancer cells compared to normal prostate cells, which is correlated with cellular migration and invasion of prostate cancer. Here, the molecular mechanisms of HDGF in prostate cancer is investigated. It is shown that HDGF knockdown reduces prostate cancer cellular migration and inv ...[more]

PMID: 29300772

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Project description:Low vitamin D status is associated with progression in patients with renal cell carcinoma (RCC). The present study found that vimentin, a mesenchymal marker, was accordingly upregulated, and E-cadherin, an epithelial marker, was downregulated in RCC patients with low vitamin D status. Thus, we investigated the effects of calcitriol or vitamin D3, an active form of vitamin D, on epithelial-mesenchymal transition (EMT) in RCC cells. RCC cells were treated by two models. In model 1, three RCC cell lines, ACHN, 786-O and CAKI-2, were incubated with either LPS (2.0 μg/mL) or transforming growth factor (TGF)-β1 (10 ng/mL) in the presence or absence of calcitriol (200 nmol/L). In model 2, two RCC cell lines, ACHN and CAKI-2, were incubated with calcitriol (200 nmol/L) only. Calcitriol inhibited migration and invasion not only in TGF-β1-stimulated but also in TGF-β1-unstimulated RCC cells. Moreover, calcitriol suppressed E-cadherin downregulation and vimentin upregulation not only in TGF-β1-stimulated but also in TGF-β1-unstimulated ACHN and CAKI-2 cells. Calcitriol attenuated LPS-induced upregulation of MMP-2, MMP-7, MMP-9, MMP-26 and urokinase-type plasminogen activator (u-PA) in ACHN cells. In addition, calcitriol blocked TGF-β1-induced nuclear translocation of ZEB1, Snail and Twist1 in ACHN and CAKI-2 cells. Mechanistically, calcitriol suppressed EMT through different signaling pathways: (i) calcitriol suppressed Smad2/3 phosphorylation by reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-β1-stimulated RCC cells; (ii) calcitriol inhibited signal transducer and activator of transcription (STAT)3 activation in LPS-stimulated RCC cells; (iii) calcitriol inhibited β-catenin/TCF-4 activation by promoting integration of VDR with β-catenin in TGF-β1-unstimulated RCC cells. Taken together, calcitriol inhibits migration and invasion of RCC cells partially by suppressing Smad2/3-, STAT3- and β-catenin-mediated EMT.

Project description:BackgroundTo examine whether MLKL participated in the invasion of radiosensitive nasopharyngeal carcinoma (NPC) cell (CNE-2) and radioresistant NPC cell (CR) through regulating epithelial-mesenchymal transition (EMT).MethodssiRNA and CRISPR/Cas9 technique were used to decrease MLKL expression in NPC cell (CNE-2 and CR). Trans-well assay was conducted to evaluate invasion. Gene expression profiling was performed using Human U133 2.0 plus arrays (Affymetrix). Kyoto Encyclopedia of Genes and Genomes (KEGG) was adopted to analyze gene expression profiling. Hub genes at a functional level were accessed by protein-to-protein network (PPI). Quantitative real-time PCR and Western blot were used to access EMT markers.ResultsInvasion of CR was about 3~fold change higher than that of CNE-2. Silencing MLKL by siRNA inhibited invasion of CR, not CNE-2. Further, depleting MLKL by CRISPR-Cas9 in CR (CR-MLKL KO) also inhibited its invasion. KEGG pathway analysis showed invasion-related pathways were altered, such as adherent junction, TGF-β signaling pathway. PPI demonstrated that compared with CNE-2, CR showed 9 elevated hub genes including EGFR, JUN, CD44, SPP1, VIM, IL-8, BCL2, WDFY2, PIK3CD and 1 downregulated hub gene CDH1. After MLKL depletion, 8 hub genes were downregulated (EGFR, JUN, CD44, SPP1, VIM, FGF13, PLAU, MMP1) and 2 hub genes were upregulated (MMP9, CDH1). Quantitative real-time PCR results showed that compared with CNE-2, CR displayed decreased epithelial markers significantly (E-Cadherin) and increased mesenchymal markers significantly (Vimentin, N-Cadherin, Zeb1), indicating irradiation-induced EMT. After depletion of MLKL in CR, the expression of E-Cadherin, Vimentin, N-Cadherin, Zeb1 was reversed to the level of CNE-2. Western blot confirmed the results from qRT-PCR.ConclusionsDepletion of MLKL efficiently inhibits invasion of radioresistant NPC by suppressing EMT. MLKL may be an important target to suppress distant metastasis of NPC patients who relapsed after radiotherapy.

Dataset Information

Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9.

Publications

Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9.

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