Identification of immediate early response protein 2 as a regulator of angiogenesis through the modulation of endothelial cell motility and adhesion

Abstract

Abstract. Human immediate early response 2 (IER2) has been characterized as a putative nuclear protein that functions as a transcription factor or transcriptional co-activator in the regulation of cellular responses, and may be involved in the regulation of tumor progression and metastasis. Data from our previous gene expression profile of the human microvascular endothelial cells during capillary morphogenesis showed a significant alteration of IER2 expression, suggesting that IER2 may participate in the regulation of the endothelial cell morphogenesis and angiogenesis. The aim of the present study was to investigate the role of IER2 in cell motility, cell-matrix adhesion and in vitro capillary-like structures formation of the human umbilical vein endothelium cells (HUVECs). IER2 was constitutively expressed in HUVECs, and lentiviral-mediated depletion of IER2 significantly reduced the cell motility, cell-matrix adhesion and capillary-like structures formation of HUVECs. Results also showed that depletion and overexpression of IER2 altered the actin cytoskeleton rearrangement in HUVECs. Furthermore, results from western blot analysis showed that the activity of the focal adhesion kinase (FAK) can be regulated by IER2. These results indicated that IER2 regulates endothelial cell motility, adhesion on collagen type I matrix and the capillary tube formation, as the result of the regulation of the actin cytoskeleton rearrangement presumably via a FAK-dependent mechanism.

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

“…Khalaj et al previously observed that TTP has the potential to regulate the inflammatory process associated with endometriosis by interacting with tumour necrosis factor alpha (TNF-α), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), hypoxia-inducible factor 1alpha (HIF-1α), and interferon gamma (IFN-γ) 128 . IER2, in addition to FOS and JUN, is an immediate early gene that can be induced by proliferation and migration stimuli, and this gene contributes to angiogenesis, cell motility, adhesion 129 , and tumour progression 130 . APOD encodes an atypical lipoprotein from the lipocalin family that is expressed in the normal endometrium 131 and is responsible for the transport of small lipophilic molecules 132 , including sexual steroidal hormones, that, in turn, modulate its translation 133,134 .…”

Immediate early response protein 2 regulates hepatocellular carcinoma cell adhesion and motility via integrin β1-mediated signaling pathway

“…Recently, evidence suggests that IER2 seems to play a pivotal role in tumor cell motility and metastasis (6), however, little is known about the mechanism involved. We have previously shown that IER2 regulated human umbilical vein endothelium cell motility, adhesion, in vitro capillary tube formation, and the actin cytoskeleton rearrangement in a FAK-dependent manner (7). Furthermore, we also found that IER2, as a direct and functional target for miR-30c in the hepatocellular carcinoma (HCC) cell lines (SMMC-7721 and HepG2 cells), may function as a positive regulator in cell migration and invasion (8), suggesting that IER2 may play a role in the HCC cell motility.…”

Perinatal findings in a patient with a novel large chromosome 19p deletion

“…LYL1 and IER2 gene products are involved in angiogenesis, capillary formation, and vessel stabilization . We speculate that the gastrointestinal tract in a patient with deletions of these genes would be more prone to tissue injury in a setting of peritonitis or surgery, as seen in our patient.…”