Abstract 3109: Myc confers aggressive medulloblastoma phenotypes by regulating cell migration and adhesion genes
Bibliographic record
Abstract
Abstract Mechanisms by which Myc confers aggressive phenotypes and adverse outcomes in medulloblastoma remain largely unknown. In this study, we demonstrate using 2 medulloblastoma cell line models that high Myc expression increases cell migration/invasion and induces metastatic orthotopic tumors which recapitulate the aggressive histology of primary anaplastic medulloblastoma. Using ChIP-chip and expression analysis on Myc transformed medulloblastoma cell lines, we identified a subset of cell migration and adhesion genes as direct Myc repressed transcriptional targets. These include ING4, PVRL3, PPAP2B and Tsp-1/THBS1, a potent tumor suppressor not previously implicated in medulloblastoma. Tsp-1 expression in medulloblastoma cell lines and primary tumors were consistently and significantly diminished in the presence of high Myc (n=101, p=0.032). Using ChIP and reporter assays we confirmed Myc and Max co-localization to a basal Tsp-1 promoter and decreased Tsp-1 transcription in the presence of Myc. Our analyses also revealed that JPO2, a Myc interacting protein linked to metastatic medulloblastoma, directly binds the Tsp-1 promoter and augments Myc-mediated Tsp-1 repression. Interestingly, we observed that stable Tsp-1 expression significantly diminished soft agar growth and drastically decreased cell invasion/migration in high-Myc expressing medulloblastoma cell lines without effects on cellular proliferation. Our collective findings highlight a novel and important role for Tsp-1 in Myc- induced metastatic medulloblastoma phenotypes and suggest Tsp-1 agonists may represent attractive, therapeutics for primary metastatic medulloblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3109.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.003 | 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".