Identification of Target Proteins for Promoting Nuclear Envelope Rupture in Cancer Cells
Bibliographic record
Abstract
The nuclear envelope separates and protects DNA from the cytoplasm. In cancer cells, frequent nuclear morphological abnormalities and transient rupture of the nuclear membrane promote DNA damage and cancer malignancy. However, nuclear envelope instability, acting as a tumor-promotion factor, can be viewed as a fatal weakness of cancer cells. Although the exact mechanism is not clear, it is known that the loss of the tumor suppressor gene TP53 is involved in nuclear envelope instability in cancer cells. In this study, we demonstrate that the inhibition of NUP93, which is a subunit of the nuclear pore complex, induces cell death by enhancing nuclear envelope instability. The RNA interference (RNAi) inhibiting NUP93 expression in the human cell line RPE1 caused nuclear envelope rupture, and DNA damage, leading to cell death. Under the condition in which the tumor suppressor gene TP53 was simultaneously suppressed with NUP93, nuclear envelope rupture and DNA damage were significantly increased. Conversely, cell death was slightly decreased. The decrease in cell death may be ascribed to the fact that TP53 is involved in the induction of apoptosis by DNA damage. We speculate that amplification of nuclear envelope instability may induce cancer cell-specific synthetic lethality in the context of TP53-independent nuclear envelope instability. Moreover, our results suggest that nuclear pore proteins can be promising targets for the development of synthetic lethal anticancer drugs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".