Article

Identification of a novel protein, LYRIC, localized to tight junctions of polarized epithelial cells.

Department of Medicine, Rhode Island Hospital/Brown University, Providence, RI 02903, USA.
Experimental Cell Research (Impact Factor: 3.37). 11/2004; 300(1):134-48. DOI: 10.1016/j.yexcr.2004.06.026
Source: PubMed

ABSTRACT Tight junctions (TJ) are multiprotein complexes that function to regulate paracellular transport of molecules through epithelial and endothelial cell layers. Many new tight junction-associated proteins have been identified in the past few years, and their functional roles and interactions have just begun to be elucidated. In this paper, we describe a novel protein LYsine-RIch CEACAM1 co-isolated (LYRIC) that is widely expressed and highly conserved between species. LYRIC has no conserved domains that would indicate function and does not appear to be a member of a larger protein family. Data from analysis of rat and human tissue sections and cell lines show that LYRIC colocalizes with tight junction proteins ZO-1 and occludin in polarized epithelial cells, suggesting that LYRIC is part of the tight junction complex. LYRIC dissociates from ZO-1 when junctional complexes are disrupted, and as tight junctions reform, ZO-1 relocalizes before LYRIC. These results suggest that LYRIC is most likely not a structural component required for TJ formation, but rather is recruited during the maturation of the tight junction complex.

0 Followers
 · 
128 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Osteosarcoma is the most common primary malignant bone tumour in children and adolescents and is characterised by high malignant and metastatic potentials. However, the molecular mechanism underlying this invasiveness remains unclear. In this study, we determined that PD98059 and SP600125, the two mitogen-activated protein kinase (MAPK) family inhibitors, decreased the osteosarcoma cell U2OS-AEG-1 migration and invasion that was enhanced by astrocyte elevated gene-1 (AEG-1) in an in vitro wound-healing and Matrigel invasion assay independently of cell viability. These findings indicate that AEG-1 promoted osteosarcoma cell invasion is relevant to the MAPK pathways. The up-regulation of AEG-1 increased the levels of phosphor-c-Jun N-terminal kinase (JNK) and phosphor-c-Jun; however, there were no marked changes in the levels of phosphor-extracellular regulated kinase (ERK) 1/2 or phosphor-c-Fos due to the activation of AEG-1 in U2OS. SP600125 (a JNK inhibitor) decreased phosphor-c-Jun and MMP-2 in U2OS-AEG-1, while PD98059 (a ERK1/2 inhibitor) had no influence on the levels of phosphor-c-Jun or MMP-2 in U2OS-AEG-1. Further study revealed that the down-regulation of phosphor-c-Jun not only obviously decreased the MMP-2 protein level and the MMP-2 transcriptional activity that were up-regulated by AEG-1 in Western-blot and luciferase reporter assays, but also inhibited the migration and invasion abilities of the U2OS-AEG-1 cells, which suggests that AEG-1 mediated U2OS invasion at least partially via the JNK/c-Jun/MMP-2 pathway. Consistent with these observations, immunohistochemical (IHC) staining revealed that AEG-1 expression was associated with the protein levels of phosphor-c-Jun and MMP-2 in needle biopsy paraffin-embedded archival human osteosarcoma tissues. Taken together, our findings suggest that AEG-1 plays a crucial role in the aggressiveness of osteosarcoma via the JNK/c-Jun/MMP-2 pathway.
    Biochemical and Biophysical Research Communications 10/2014; 452(4). DOI:10.1016/j.bbrc.2014.09.009 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Metadherin (MTDH) has been identified as an important oncogene in carcinogenesis, tumor progression and metastasis in numerous malignancies, through signal transduction pathways. MTDH is a potential biomarker and therapeutic target in cancers. The present systematic review was performed to search for studies regarding MTDH and prostate, bladder and kidney cancer using several databases and the eligible studies were reviewed. MTDH expression was found to significantly increase in prostate, bladder and kidney cancers, not only in clinical tissue samples, but also in cancer cell lines. Reviewing the clinical and statistical analysis revealed that MTDH may be involved in urologic cancer progression, metastasis and prognosis. MTDH may be an independent or one of the cofactors in urologic cancers for prediction of patient survival, and may be involved in potential anticancer strategies. MTDH may be associated with several signal transduction pathways in urologic cancers, indicating latent targets to develop anticancer therapeutic strategy. Further studies are required to confirm these findings.
    Molecular and Clinical Oncology 11/2014; 2(6):1139-1144. DOI:10.3892/mco.2014.392
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Astrocyte elevated gene-1 (AEG-1) plays important roles in tumorigenesis such as proliferation, invasion, metastasis, angiogenesis, and chemoresistance. We examined the expression of AEG-1 in patients with hepatocellular carcinoma (HCC). Eighty-five samples were collected from patients with HCC who underwent surgery and were histopathologically confirmed to have HCC. Two independent pathologists, experienced in evaluating immunohistochemistry and blinded to the clinical outcomes of the patients, reviewed all samples. They determined AEG-1 expression semiquantitatively by assessing the percentage of positively stained immunoreactive cells and staining intensity. Clinicopathological data were analyzed in association with prognosis. The association was estimated by univariate and multivariate analyses with Cox regression. Tumor size (hazard ratio [HR], 2.285; 95% confidence interval [CI], 1.175-4.447; P = 0.015), microvascular invasion (HR, 6.754; 95% CI, 1.631-27.965; P = 0.008), and AEG-1 expression (HR, 4.756; 95% CI, 1.697-13.329; P = 0.003) were independent prognostic factors for overall survival. Those for disease-free survival rate were tumor size (HR, 2.245; 95% CI, 1.282-3.933; P = 0.005) and AEG-1 expression (HR, 1.916; 95% CI, 1.035-3.545; P = 0.038). The cumulative 5-year survival and recurrence rates were 89.2% and 50.0% in the low-expressing group and 24.5% and 82.4% in the high-expressing group, respectively. The results suggest that AEG-1 overexpression could serve as a valuable prognostic marker in patients with HCC.
    02/2015; 88(2):77-85. DOI:10.4174/astr.2015.88.2.77

Full-text (2 Sources)

Download
67 Downloads
Available from
May 23, 2014