Signal transduction induced in endothelial cells by growth factor receptors involved in angiogenesis

Hofer, Erhard; Schweighofer, Bernhard

doi:10.1160/th06-08-0470

Cited by 83 publications

(38 citation statements)

References 111 publications

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“…Tumor angiogenesis principally relies on vascular endothelial growth factor (VEGF)-driven angiogenic responses, which lead to a dysfunctional vasculature [[70]]. Moreover, the invasion of endothelial cells (ECs) occurs after the release of matrix metalloproteinase 2 and 9 (MMP2/9), which destroy and degrade the basal membrane and extracellular matrix, finally resulting in the migration of ECs and the formation of neovessels [[71]].…”

Section: Introductionmentioning

confidence: 99%

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

Chu

Duan

et al. 2014

Cell Commun Signal

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The pathogenesis of hepatocellular carcinoma (HCC) is not fully understood, which has affected the early diagnosis and treatment of HCC and the survival time of patients. MicroRNAs (miRNAs) are a class of evolutionarily conserved small, non-coding RNAs, which regulate the expression of various genes post-transcriptionally. Emerging evidence indicates that the key enzymes involved in the miRNA biosynthesis pathway and some tumor-specific miRNAs are widely deregulated or upregulated in HCC and closely associated with the occurrence and development of various cancers, including HCC. Early studies have shown that miRNAs have critical roles in HCC progression by targeting many critical protein-coding genes, thereby contributing to the promotion of cell proliferation; the avoidance of apoptosis, inducing via angiogenesis; and the activation of invasion and metastasis pathways. Experimental data indicate that discovery of increasing numbers of aberrantly expressed miRNAs has opened up a new field for investigating the molecular mechanism of HCC progression. In this review, we describe the current knowledge about the roles and validated targets of miRNAs in the above pathways that are known to be hallmarks of HCC, and we also describe the influence of genetic variations in miRNA biosynthesis and genes.

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Section: Introductionmentioning

confidence: 99%

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

Chu

Duan

et al. 2014

Cell Commun Signal

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“…Tip cells migrate out of the vessel wall followed by proliferating stalk cells eventually forming a new capillary [3]. VEGF-A/VEGFR2 signaling has been shown to strongly activate the PKC/MAPK and Ca ++ /NFAT pathways via PLC-gamma as well as the PI3K/AKT pathway to induce migration, proliferation and survival [4], [5].…”

Section: Introductionmentioning

confidence: 99%

The Transcription Factor MEF2C Negatively Controls Angiogenic Sprouting of Endothelial Cells Depending on Oxygen

et al. 2014

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The MADS box transcription factor MEF2C has been detected by us to be upregulated by the angiogenic factors VEGF-A and bFGF in endothelial cells. We have here investigated its potential role for angiogenesis. MEF2C was surprisingly found to strongly inhibit angiogenic sprouting, whereas a dominant negative mutant rather induced sprouting. The factor mainly affected migratory processes of endothelial cells, but not proliferation. In gene profiling experiments we delineated the alpha-2-macroglobulin gene to be highly upregulated by MEF2C. Further data confirmed that MEF2C in endothelial cells indeed induces alpha-2-macroglobulin mRNA as well as the secretion of alpha-2-macroglobulin and that conditioned supernatants of cells overexpressing MEF2C inhibit sprouting. Alpha-2-macroglobulin mediates, at least to a large extent, the inhibitory effects of MEF2C as is shown by knockdown of alpha-2-macroglobulin mRNA by lentiviral shRNA expression which reduces the inhibitory effect. However, under hypoxic conditions the VEGF-A/bFGF-mediated upregulation of MEF2C is reduced and the production of alpha-2-macroglobulin largely abolished. Taken together, this suggests that the MEF2C/alpha-2-macroglobulin axis functions in endothelial cells as a negative feed-back mechanism that adapts sprouting activity to the oxygen concentration thus diminishing inappropriate and excess angiogenesis.

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“…PLC-γ in turn leads to calcium release and activation of protein kinase C (PKC) pathways. These pathways induce the transcription factors NFAT and EGR-1, respectively, to trigger the angiogenic response (Hofer and Schweighofer, 2007; Machtcheriakova et al, 1999; Mechtcheriakova et al, 2001). PLC-γ/PKC also activate protein kinase D (PKD) phosphorylation of histone deacetylase 7 (HDAC7) resulting in endothelial cell proliferation and migration (Wang et al, 2008).…”

Section: Signaling In Vasculogenesismentioning

confidence: 99%

“…However, other studies suggested a mitogenic role for TGFβ on endothelial cells (Iruela-Arispe and Sage, 1993; RayChaudhury and D’Amore, 1991; Sutton et al, 1991). These differences in TGFβ action could be due to differences in dose since low doses of TGFβ upregulate angiogenic factors, whereas high doses appear to inhibit endothelial cell growth (Hofer and Schweighofer, 2007). Contradictory results were also observed in vivo with studies showing both pro-angiogenic and anti-angiogenic roles for TGFβ (Li et al, 2001; Roberts et al, 1986).…”

Section: Signaling In Vasculogenesismentioning

confidence: 99%

Signal transduction in vasculogenesis and developmental angiogenesis

Patel–Hett

D'Amore²

2011

Int. J. Dev. Biol.

182

151

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The vasculature is a highly specialized organ that functions in a number of key physiological tasks including the transport of oxygen and nutrients to tissues. Formation of the vascular system is an essential and rate-limiting step in development and occurs primarily through two main mechanisms, vasculogenesis and angiogenesis. Both vasculogenesis, the de novo formation of vessels, and angiogenesis, the growth of new vessels from pre-existing vessels by sprouting, are complex processes that are mediated by the precise coordination of multiple cell types to form and remodel the vascular system. A host of signaling molecules and their interaction with specific receptors are central to activating and modulating vessel formation. This review article summarizes the current state of research involving signaling molecules that have been demonstrated to function in the regulation of vasculogenesis and angiogenesis, as well as molecules known to play a role in vessel maturation, hypoxia-driven angiogenesis and arterial-venous specification.

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Signal transduction induced in endothelial cells by growth factor receptors involved in angiogenesis

Cited by 83 publications

References 111 publications

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

The Transcription Factor MEF2C Negatively Controls Angiogenic Sprouting of Endothelial Cells Depending on Oxygen

Signal transduction in vasculogenesis and developmental angiogenesis

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