Abstract 1185: Plakoglobin (β-catenin) interacts with the transcription factor p53 and regulates the expression of genes involved in tumorigenesis and metastasis
Bibliographic record
Abstract
Abstract Plakoglobin (β-catenin) and β-catenin are highly homologous proteins that function in cell-cell adhesion and signaling. Both proteins exist in a cadherin-associated form, which mediates adhesion, and in a distinct cytosolic/nuclear form, which plays a signaling role. Despite their interactions with common cellular partners, β-catenin has well documented oncogenic potential while plakoglobin expression is generally associated with tumor/metastasis suppression. The underlying mechanisms for this activity of plakoglobin are unclear. We previously showed that plakoglobin expression in oral squamous carcinoma cells (SCC9-PG) resulted in a mesenchymal-epidermoid transition, which was concurrent with increased N-cadherin and decreased β-catenin levels. Comparison of the RNA and protein profiles of SCC9 cells and SCC9-PG transfectants identified a number of differentially expressed proteins and transcripts, which suggested that plakoglobin regulates gene expression. Closer analysis of the mRNA profiles of SCC9 and SCC9-PG cells identified several p53 target genes that were differentially expressed upon plakoglobin expression, suggesting that plakoglobin may regulate gene expression in conjunction with p53. Here, we describe the ability of plakoglobin to regulate three potential p53 target genes: the tumor and metastasis suppressors 14-3-3α and Nm23 and the tumor promoter SATB1. We show, by RT-PCR and Western blot, that plakoglobin expression results in increased 14-3-3σ and Nm23 and decreased SATB1 mRNA and protein levels. Co-immunoprecipitation experiments show that plakoglobin and p53 interact, and that these interactions occur in both the cytoplasm and the nucleus. Chromatin immunoprecipitation and Electrophoretic mobility shift assays (EMSA) indicate that plakoglobin and p53 associate with the promoters of these target genes. Finally, luciferase reporter assays confirm that plakoglobin regulates the expression of these p53 target genes. Taken together, the results of these studies provide strong evidence that plakoglobin plays an active role in regulating gene expression, a function that has not often been associated with plakoglobin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1185. doi:1538-7445.AM2012-1185
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".