Dataset Information

Prostaglandin E2 stimulates ?1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-?B pathway.

ABSTRACT: Prostaglandin E2 (PGE2) has been implicated in cell invasion in hepatocellular carcinoma (HCC), via increased ?1-integrin expression and cell migration; however, the mechanism remains unclear. PGE2 exerts its effects via four subtypes of the E prostanoid receptor (EP receptor 1-4). The present study investigated the effect of EP1 receptor activation on ?1-integrin expression and cell migration in HCC. Cell migration increased by 60% in cells treated with 17-PT-PGE2 (EP1 agonist), which was suppressed by pretreatment with a ?1-integrin polyclonal antibody. PGE2 increased ?1-integrin expression by approximately 2-fold. EP1 receptor transfection or treatment with 17-PT-PGE2 mimicked the effect of PGE2 treatment. EP1 siRNA blocked PGE2-mediated ?1-integrin expression. 17-PT-PGE2 treatment induced PKC and NF-?B activation; PKC and NF-?B inhibitors suppressed 17-PT-PGE2-mediated ?1-integrin expression. FoxC2, a ?1-integrin transcription factor, was also upregulated by 17-PT-PGE2. NF-?B inhibitor suppressed 17-PT-PGE2-mediated FoxC2 upregulation. Immunohistochemistry showed p65, FoxC2, EP1 receptor and ?1-integrin were all highly expressed in the HCC cases. This study suggested that PGE2 upregulates ?1-integrin expression and cell migration in HCC cells by activating the PKC/NF-?B signaling pathway. Targeting PGE2/EP1/PKC/NF-?B/FoxC2/?1-integrin pathway may represent a new therapeutic strategy for the prevention and treatment of this cancer.

SUBMITTER: Bai X

PROVIDER: S-EPMC5377465 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prostaglandin E2 stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway.

Bai Xiaoming X Wang Jie J Guo Yan Y Pan Jinshun J Yang Qinyi Q Zhang Min M Li Hai H Zhang Li L Ma Juan J Shi Feng F Shu Wei W Wang Yipin Y Leng Jing J

Scientific reports 20141007

Prostaglandin E2 (PGE2) has been implicated in cell invasion in hepatocellular carcinoma (HCC), via increased β1-integrin expression and cell migration; however, the mechanism remains unclear. PGE2 exerts its effects via four subtypes of the E prostanoid receptor (EP receptor 1-4). The present study investigated the effect of EP1 receptor activation on β1-integrin expression and cell migration in HCC. Cell migration increased by 60% in cells treated with 17-PT-PGE2 (EP1 agonist), which was suppr ...[more]

PMID: 25289898

Similar Datasets

Project description:Inflammatory mechanisms mediated by prostaglandins may contribute to the progression of intracerebral hemorrhage (ICH)-induced brain injury, but they are not fully understood. In this study, we examined the effect of prostaglandin E2 receptor EP1 (EP1R) activation and inhibition on brain injury in mouse models of ICH and investigated the underlying mechanism of action. ICH was induced by injecting collagenase, autologous blood, or thrombin into the striatum of middle-aged male and female mice and aged male mice. Effects of selective EP1R agonist ONO-DI-004, antagonist SC51089, and nonspecific Src family kinase inhibitor PP2 were evaluated by a combination of histologic, magnetic resonance imaging (MRI), immunofluorescence, molecular, cellular, and behavioral assessments. EP1R was expressed primarily in neurons and axons but not in astrocytes or microglia after ICH induced by collagenase. In middle-aged male mice subjected to collagenase-induced ICH, EP1R inhibition mitigated brain injury, brain edema, cell death, neuronal degeneration, neuroinflammation, and neurobehavioral deficits, whereas its activation exacerbated these outcomes. EP1R inhibition also was protective in middle-aged female mice and aged male mice after collagenase-induced ICH and in middle-aged male mice after blood- or thrombin-induced ICH. EP1R inhibition also reduced oxidative stress, white matter injury, and brain atrophy and improved functional outcomes. Histologic results were confirmed by MRI. Src kinase phosphorylation and matrix metalloproteinase-9 activity were increased by EP1R activation and decreased by EP1R inhibition. EP1R regulated matrix metalloproteinase-9 activity through Src kinase signaling, which mediated EP1R toxicity after collagenase-induced ICH. We conclude that prostaglandin E2 EP1R activation plays a toxic role after ICH through mechanisms that involve the Src kinases and the matrix metalloproteinase-9 signaling pathway. EP1R inhibition could be a novel therapeutic strategy to improve outcomes after ICH.

Dataset Information

Prostaglandin E2 stimulates ?1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-?B pathway.

Publications

Prostaglandin E2 stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets