Dataset Information

Integrin regulation of beta-catenin signaling in ovarian carcinoma.

ABSTRACT: Reversible modulation of integrin-regulated cell-matrix adhesion and epithelial (E)-cadherin-mediated cell-cell adhesion plays a critical role in the establishment of ovarian cancer metastases. In contrast to most epithelial cell-derived tumors that down-regulate E-cadherin expression during progression, acquisition of E-cadherin expression accompanies malignant transformation of the ovarian surface epithelium and is maintained in peritoneal metastases. Metastatic epithelial ovarian cancer cells are disseminated intraperitoneally and preferentially adhere via integrins to interstitial collagens in the peritoneal cavity. This study was undertaken to determine whether integrin engagement influences E-cadherin and ?-catenin localization and function. The data demonstrate that multivalent integrin engagement results in increased internalization of E-cadherin, inhibition of GSK-3?, elevated levels of nuclear ?-catenin, increased ?-catenin-regulated promoter activation, and transcriptional activation of Wnt/?-catenin target genes. Blocking ?-catenin transcriptional control with inhibitor of ?-catenin and Tcf-4 reduces cellular invasion, suggesting a key role for ?-catenin nuclear signaling in EOC invasion and metastasis. These studies support a model wherein cell-matrix engagement regulates the functional integrity of cell-cell contacts, leading to increased ?-catenin nuclear signaling and enhanced cellular invasive activity. Furthermore, these results provide a mechanism for activation of Wnt/?-catenin signaling in the absence of activating mutations in this pathway.

SUBMITTER: Burkhalter RJ

PROVIDER: S-EPMC3123110 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrin regulation of beta-catenin signaling in ovarian carcinoma.

Burkhalter Rebecca J RJ Symowicz Jaime J Hudson Laurie G LG Gottardi Cara J CJ Stack M Sharon MS

The Journal of biological chemistry 20110425 26

Reversible modulation of integrin-regulated cell-matrix adhesion and epithelial (E)-cadherin-mediated cell-cell adhesion plays a critical role in the establishment of ovarian cancer metastases. In contrast to most epithelial cell-derived tumors that down-regulate E-cadherin expression during progression, acquisition of E-cadherin expression accompanies malignant transformation of the ovarian surface epithelium and is maintained in peritoneal metastases. Metastatic epithelial ovarian cancer cells ...[more]

PMID: 21518759

Similar Datasets

Project description:BackgroundDeregulation of Wnt/β-catenin signaling is a hallmark of the majority of sporadic forms of colorectal cancer and results in increased stability of the protein β-catenin. β-catenin is then shuttled into the nucleus where it activates the transcription of its target genes, including the proto-oncogenes MYC and CCND1 as well as the genes encoding the basic helix-loop-helix (bHLH) proteins ASCL2 and ITF-2B. To identify genes commonly regulated by β-catenin in colorectal cancer cell lines, we analyzed β-catenin target gene expression in two non-isogenic cell lines, DLD1 and SW480, using DNA microarrays and compared these genes to β-catenin target genes published in the PubMed database and DNA microarray data presented in the Gene Expression Omnibus (GEO) database.ResultsTreatment of DLD1 and SW480 cells with β-catenin siRNA resulted in differential expression of 1501 and 2389 genes, respectively. 335 of these genes were regulated in the same direction in both cell lines. Comparison of these data with published β-catenin target genes for the colon carcinoma cell line LS174T revealed 193 genes that are regulated similarly in all three cell lines. The overlapping gene set includes confirmed β-catenin target genes like AXIN2, MYC, and ASCL2. We also identified 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that are regulated similarly in DLD1 and SW480 cells and one pathway - the steroid biosynthesis pathway - was regulated in all three cell lines.ConclusionsBased on the large number of potential β-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T cells as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study Wnt/β-catenin signaling and associated colorectal carcinogenesis. Furthermore, the confirmed and the newly identified potential β-catenin target genes are useful starting points for further studies.

Dataset Information

Integrin regulation of beta-catenin signaling in ovarian carcinoma.

Publications

Integrin regulation of beta-catenin signaling in ovarian carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure