AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration

Park, Kyoungsook; Chung, Yoo Seung; So, Hyekyung; Kim, Kwangsoo; Park, Junsoo; Oh, Mi-Jung; Jo, MinWha; Choi, Kae Won; Lee, Eun Ju; Choi, Yoon La; Song, Sang Yong; Bae, Duk Soo; Kim, Byoung Gie; Lee, Je Ho

doi:10.3858/emm.2011.43.2.011

Cited by 75 publications

(71 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also of interest are AGR2, KRT8, and SFN. AGR2 is a known proto-oncogene recently confirmed to be overexpressed in lung adenocarcinoma (Pizzi et al 2012), and has been shown to promote cell proliferation and migration in several different cancers (Ramachandran et al 2008;Vanderlaag et al 2010;Park et al 2011). KRT8, encoding keratin 8, was previously reported to be up-regulated in lung adenocarcinoma (Wikman et al 2002); and SFN, encoding stratifin, has been reported to be overexpressed in early invasive lung adenocarcinoma (Shiba-Ishii et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression

Selamat¹,

Chung²,

Girard³

et al. 2012

Genome Res.

443

394

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung pairs, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent down-regulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways, and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and down-regulated in smokers.LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by identifying novel epigenetically deregulated genes potentially involved in lung adenocarcinoma development/progression, and by describing an epigenetic subgroup of lung adenocarcinoma associated with characteristic molecular alterations.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression

Selamat¹,

Chung²,

Girard³

et al. 2012

Genome Res.

443

394

View full text Add to dashboard Cite

show abstract

“…Because Agr2 is present in the serum and urine of some patients with cancer (21,22), it must be secreted into the extracellular space. We detected Agr2 in conditioned medium of Tu-katoIII and HSC-39 cells, but not in the conditioned medium of Agr2miR cells (Fig.…”

Section: Agr2 Is Secreted From Gastric Srcc Cells and Incorporated Inmentioning

confidence: 99%

“…This motif interacts with the receptor in ER membrane that binds proteins with the terminal KDEL ER retention sequence, leading to ER localization of Agr2 (20). In some types of cancer, however, Agr2 is also present in the extracellular space, serum, and urine (21,22). Although Agr2 is known to exert angiogenic effect (23), the functions of extracellular Agr2 are not as well characterized as the protein's roles in the ER.…”

Section: Introductionmentioning

confidence: 99%

Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells

et al. 2015

View full text Add to dashboard Cite

Agr2 is a disulfide isomerase residing in the endoplasmic reticulum (ER), which physiologically regulates protein folding and mediates resistance to ER stress. Agr2 is overexpressed in adenocarcinomas of various organs, where it participates in neoplastic transformation and metastasis, therefore acts as a pro-oncogenic protein. Besides its normal localization in the ER, Agr2 is also found in the serum and urine of cancer patients, although the physiological significance of extracellular Agr2 is poorly understood. In this study, we demonstrated that extracellular Agr2 can activate stromal fibroblasts and promote fibroblastassociated cancer invasion in gastric signet-ring cell carcinoma (SRCC), where Agr2 is highly expressed. Agr2 secreted from SRCC cells was incorporated by the surrounding gastric fibroblasts and promoted invasion by these cells. In turn, activated fibroblasts coordinated the invasive behavior of fibroblasts and cancer cells. Our findings suggested that Agr2 drives progression of gastric SRCC by exerting paracrine effects on fibroblasts in the tumor microenvironment, acting also to increase the growth and resistance of SRCC cells to oxidative and hypoxic stress as cell autonomous effects. Cancer Res; 75(2); 356-66. Ó2014 AACR.

show abstract

“…A previous study demonstrated that THBS1 expression is associated with, and may function as a biomarker for the prognosis of, ovarian cancer (25). Another study demonstrated that downregulating THBS1 in ovarian cancer promotes tumor migration (26). According to comparative proteomic analysis, THBS1 is associated with cell adhesion, and differentially expressed between low malignant potential and highly proliferative EOC cell lines (27).…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers for epithelial ovarian cancer metastasis using microarray data

Xu³

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. Epithelial ovarian cancer (EOC) is a common cancer in women worldwide. The present study assessed effective biomarkers for the prognosis of EOC metastasis. The GSE30587 dataset, containing 9 EOC primary tumor samples and 9 matched omental metastasis samples, was analyzed. Following normalization, the differentially expressed genes (DEGs) between these samples were identified using the limma package for R. Subsequently, pathway enrichment analysis was performed using ClueGO, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database. The microRNA (mRNA/miR)-target network was established using the multiMiR package. A set of 272 DEGs was identified in metastatic EOC samples, including 189 upregulated and 83 downregulated genes. Collagen type I α 1 chain (COL1A1), COL1A2, collagen type XI α 1 chain (COL11A1) and thrombospondin (THBS)1 were enriched in the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), focal adhesion and extracellular matrix (ECM)-receptor interaction signaling pathways. THBS1 and tissue inhibitor of metalloproteinase (TIMP)3 were two dominant nodes in the PPI network and were key in the miRNA-target network, being targeted by hsa-miR-1. Multiple DEGs and miRNAs were identified as potential biomarkers for the prognosis of EOC metastasis in the present study, which likely affected metastasis by regulating the PI3K/Akt, ECM-receptor interaction and cell adhesion signaling pathways. In addition, THBS1 and TIMP3 were identified as potential targets of hsa-miR-1.

show abstract

AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration

Cited by 75 publications

References 23 publications

Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression

Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression

Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells

Identification of candidate biomarkers for epithelial ovarian cancer metastasis using microarray data

Contact Info

Product

Resources

About