CNSC-32. ACTIN SUBUNIT STRUCTURAL DIVERSITY IN SHH MEDULLOBLASTOMA: IMPLICATIONS FOR CANCER BIOLOGY AND NEURODEVELOPMENT
Bibliographic record
Abstract
Abstract BACKGROUND Altered expression of actin subunits is found in multiple cancers. Alpha-cardiac actin (ACTC1) is expressed in sonic hedgehog medulloblastoma (SHH MB) and regulates both cell survival and migration. We hypothesized that cardiac actin has a unique structural and functional role in SHH MB and may be expressed in post-natal granule cell progenitors (GCPs) which share similar gene expression profiles. METHODS Actin subunit protein expression (ACTC1, ACTB, ACTG1, and ACTA2) was evaluated by mRNA expression profiling within established datasets and across MB cell lines by Western blot (WB). Immunofluorescence microscopy was performed to assess intracellular actin subunit localization. The composition of each subunit in filamentous (F-) actin was evaluated. Furthermore immunoprecipitation of filamentous ACTC1 was performed to assess protein-protein interactions. The ratio of F-actin to globular (G-) actin was determined by WB in SHH MB cells exposed to mitotic inhibitor. Cell viability was determined by colony formation following over-expression of dominant-negative mutant ACTC1 (P116C & G247D). RESULTS ACTC1, ACTG1, and ACTB are the predominant actin subunits in SHH MB. Immunofluorescence microscopy demonstrated co-localization of ACTC1 with ACTG1 and ACTB but not ACTA2. ACTC1 showed a unique cortical localization pattern. Post-natal MATH1 positive mouse GCPs (P3-5) demonstrate similar distribution of ACTC1 in cortical F-actin. WB analysis of ACTC1 pulldown from SHH MB cell F-actin fractions showed co-precipitation with ACTG1 and ACTB but not ACTA2. ACTC1 F-actin to G-actin ratio is maintained in cells that show resistance to mitotic inhibition. Expression of mutant ACTC1 G247D resulted in reduced cell survival. CONCLUSIONS ACTC1 subunit is incorporated into F-actin in SHH MB and GCPs. Filamentous ACTC1 forms a protein complex with ACTG1 and ACTB. Disruption of ACTC1 polymerization results in reduced cell survival. These findings suggest a functional role of ACTC1 in both SHH MB and in GCPs which are important in cerebellar development.
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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) | 0.001 | 0.000 |
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".