Lack of Fas antagonism by Met in human fatty liver disease

Zou, Chunbin; Ma, Jinlong; Wang, Xue; Guo, Lei; Zhu, Zhenqi; Stoops, John; Eaker, Amanda E.; Johnson, Carla J.; Strom, Stephen C.; Michalopoulos, George K.; DeFrances, Marie C.; Zarnegar, Reza

doi:10.1038/nm1625

Cited by 85 publications

(72 citation statements)

References 34 publications

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“…Thus, it is speculated that proliferation of liver cells might be inhibited due to the intense stimulation of CCl 4 and alcohol in this study. The oncogene MET played an important part in preventing Fas-mediated apoptosis of hepatocytes (Zou et al, 2007), and proliferation and survival of hepatocytes were impaired in mice with Met mutants after partial hepatectomy (Borowiak et al, 2004). Consistent with the above results, this study showed that the down-regulation of MET at 9 weeks may activate cell death of hepatocytes and its up-regulation at 9 weeks may suppress proliferation of liver cells.…”

Section: Discussionsupporting

confidence: 87%

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Wang¹,

Zhao²,

Chen³

et al. 2017

Afr. J. Biotechnol.

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Liver cirrhosis (LC) is a kind of liver disease which is pathologically characterized by abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. To explore the mechanism of LC occurrence at the level of mRNA, Rat Genome 230 2.0 Array was used to detect gene expression profiles of rat fibrotic livers in 3, 6 and 9 weeks after CCl 4 treatment in this study. It was found that a total of 305 genes including 153 up-regulated, 150 down-regulated and 2 up/down-regulated genes, were related to LC occurrence. Then, k-means clustering was employed to classify above 305 genes into 5 clusters based on gene expression similarity, and EASE analysis further indicated that the above genes were mainly associated with metabolic process, stress reaction, cell growth and apoptosis/death. Thereafter, ingenuity pathway analysis (IPA) software was used to analyze potential effects of the above-mentioned 305 genes, and the results suggested that lipid metabolism and cell growth were inhibited while cell apoptosis/death was activated, but immune/inflammatory response was first activated and then inhibited. Furthermore, IPA also predicted that several signal pathways "ERK/MAPK Signaling", "p38 MAPK", "Endothelin-1 Signaling", "Growth Hormone Signaling", "LPS/IL-1-mediated inhibition of RXR function" and "IL-6 Signaling" were involved in regulating the occurrence of liver cirrhosis. It was concluded that 305 genes and 3 kinds of physiological activities were closely related to LC occurrence.

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Section: Discussionsupporting

confidence: 87%

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Wang¹,

Zhao²,

Chen³

et al. 2017

Afr. J. Biotechnol.

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“…PARP1 and PARP2 proteins were first characterized as DNA repair factors that mainly respond to DNA damage and maintain the chromatin structure and integrity. Recent studies have established that PARPs serve as transcriptional enhancers and coactivators (24,34,35). Our functional experiments support the notion that C/EBP-β1 and PARPs cooperate with each other and activate the HGF gene promoter (Figure 6, A-C).…”

Section: Figuresupporting

confidence: 88%

“…This was verified by western blot using an antibody against PARP that recognizes both isoforms of PARP (PARP1 and PARP2; Figure 5D). PARPs are potent activators of gene transcription via their ability to open chromatin by polyribosylation of histones (24). We then investigated the effects of gradual loss of DATE truncation on C/EBP-β1 and PARPs binding to the promoter region to determine the minimum numbers of As that need to be deleted from DATE to enhance factor binding.…”

Section: Truncation Mutation Of Date In the Hgf Gene Promoter Region mentioning

confidence: 99%

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Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer

Ma¹,

DeFrances²,

Zou³

et al. 2009

J. Clin. Invest.

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The HGF gene is transcriptionally silenced in normal differentiated breast epithelial cells, but its repression fails to occur in mammary carcinoma tissues and cell lines. The molecular mechanisms underpinning aberrant HGF expression in breast cancer cells are unknown. Here we report the discovery of a DNA element located 750 bp upstream from the transcription start site in the human HGF promoter that acts as a transcriptional repressor and is a target of deletion mutagenesis in human breast cancer cells and tissues. This HGF promoter element consists of a mononucleotide repeat of 30 deoxyadenosines (30As), which we have termed "deoxyadenosine tract element" (DATE). Functional studies revealed that truncation mutations within DATE have profound local and global effects on the HGF promoter region by modulating chromatin structure and DNA-protein interactions, leading to constitutive activation of the HGF promoter in human breast carcinoma cell lines. We found that 51% of African Americans and 15% of individuals of mixed European descent with breast cancer harbor a truncated DATE variant (25As or fewer) in their breast tumors and that the truncated allele is associated with cancer incidence and aberrant HGF expression. Notably, breast cancer patients with the truncated DATE variant are substantially younger than those with a wild-type genotype. We also suggest that DATE may be used as a potential genetic marker to identify individuals with a higher risk of developing breast cancer.

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“…MET also interacts with the death receptor Fas, which maintains homeostasis in many tissues. MET is able to prevent Fas-mediated apoptosis in hepatocytes by sequestering Fas Zou et al 2007). This is a novel relationship between growth factor receptors and cytokine receptors in controlling apoptosis.…”

Section: Gab1 Gab1 H G F / S F H G F / S F Hgf/sfmentioning

confidence: 99%

MET: A Critical Player in Tumorigenesis and Therapeutic Target

Graveel

Tolbert

Woude

2013

Cold Spring Harbor Perspectives in Biology

108

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Since its discovery more than 25 years ago, numerous studies have established that the MET receptor is unique among tyrosine kinases. Signaling through MET is necessary for normal development and for the progression of a wide range of human cancers. MET activation has been shown to drive numerous signaling pathways; however, it is not clear how MET signaling mediates diverse cellular responses such as motility, invasion, growth, and angiogenesis. Great strides have been made in understanding the pleotropic aspects of MET signaling using three-dimensional molecular structures, cell culture systems, human tumors, and animal models. These combined approaches have driven the development of MET-targeted therapeutics that have shown promising results in the clinic. Here we examine the unique features of MET and hepatocyte growth factor/scatter factor (HGF/SF) structure and signaling, mutational activation, genetic mouse models of MET and HGF/SF, and MET-targeted therapeutics.

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Lack of Fas antagonism by Met in human fatty liver disease

Cited by 85 publications

References 34 publications

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer

MET: A Critical Player in Tumorigenesis and Therapeutic Target

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