Characterization and functional implications of the interaction between the coxsackievirus and adenovirus receptor (CAR) and beta-catenin
Bibliographic record
Abstract
AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore A66 Cancer cells commonly lose expression of cell adhesion molecules, such as E-cadherin and CEACAM1, with disease progression. Re-introduction of these molecules into high-grade cell lines results in suppression of tumor growth and invasion. To elicit this change in malignant behavior, these adhesion molecules require an intact cytoplasmic domain. Invasion suppression necessitates interaction of the cytoplasmic tail with specific intracellular proteins; simple cell adhesion is not sufficient to abrogate invasion. The Coxsackievirus and Adenovirus Receptor (CAR) is a recently identified cell adhesion molecule whose expression is downregulated in cancer progression. It is a 46-kDa transmembrane protein of the immunoglobulin superfamily of cell adhesion molecules. It was initially identified as a receptor for the attachment of group B coxsackievirus and adenovirus. Recently, CAR has been shown to have an endogenous role in suppressing cancer cell growth and invasion in prostate and bladder cancer and gliomas. Our laboratory has shown that CAR behaves much like other cell adhesion molecules in a glioblastoma multiforme (GBM) model: (1) Re-introduction into GBM cell lines reduces invasive potential. (2) An intact cytoplasmic domain is required for abrogation of invasion. We have searched for proteins which interact with its cytoplasmic domain. We have used proteomic analysis to identify proteins that bind to a GST-CAR fusion protein comprised of the cytoplasmic domain of CAR. A potential candidate is beta-catenin. Beta-catenin had previously been shown to interact with CAR. We have verified this interaction with our own affinity pulldown assay. We have confirmed that CAR directly binds beta-catenin through direct binding assays and mapped the region of interaction on both proteins. We postulate that CAR-beta-catenin interaction may function by altering beta-catenin nuclear localization and subsequent downstream gene expression. Cell fractionation studies show that nuclear beta-catenin levels are altered in CAR-expressing U87 glioma cells (U87CAR) compared to control U87LNCX cells. Our data suggest that CAR may be affecting nuclear beta-catenin levels either through manipulation of its rate of nuclear export/import or through cytoplasmic sequestration. As beta-catenin is at the crossroads of cell adhesion, migration, and growth, this interaction provides a tangible mechanism for CAR’s anti-invasive and anti-tumorigenic properties.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".