HMGA2 inhibits apoptosis through interaction with ATR/CHK1 signaling complex in human cancer cells
Bibliographic record
Abstract
Non‐histone chromatin‐binding High Mobility Group AT‐hook protein‐2 (HMGA2) is expressed in embryonic stem cells, absent in normal adult cells but re‐expressed in cancer cells. HMGA2 enhances chemoresistance and DNA base excision repair. Cancer cell models were treated with DNA‐damaging Methyl Methane Sulfonate (MMS) and let to recover. DNA damage was confirmed by immunofluorescence for γ‐H2AX and Comet assays. Upon MMS insult and during recovery, HMGA2 clones displayed significantly less γ‐H2AX foci, shorter comet tails and increased and sustained phosphorylation of CHK1 (pCHK1 S296 ) and ATR (pATR S428 ). Sustained presence of pCHK1 S296 and pATR S428 was dependent on the presence of HMGA2. Presence of pCHK1 S296 coincided with a prolonged G2/M arrest in HMGA2 clones. CHK1 knockdown in MMS‐treated HMGA2+ cancer cells resulted in a significant increase in apoptosis that was enhanced further by knockdown of HMGA2 and HMGA2 was found to be a novel interacting partner with ATR and CHK1. In conclusion, upon DNA damage, HMGA2 (i) sustained activation of pCHK1 signaling, (ii) prolonged G2/M arrest, (iii) inhibited apoptosis and (iv) interacted with members of the ATR signaling cascade. Small inhibitors attenuating HMGA2 function may be a novel therapeutic strategy to target HMGA2+ cancers. This research was supported by NSERC and Surgery Research Fund.
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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) | 0.002 | 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".