Crosstalk Between the Oncoproteins of High‐Risk Human Papillomaviruses Types 16 and 18 in Colorectal Cancer Cell Models
Bibliographic record
Abstract
BACKGROUND: Colorectal cancer (CRC) represents a major fraction of the total cancer burden worldwide. It has been recently identified that various high-risk Human Papillomaviruses (HPVs) are present in human CRCs, where they play a critical role in the development and progression of the cancer. AIMS: In this study, we explored the synergistic effect of the E6/E7 viral oncoproteins of the two most frequently observed HPV types (16 and 18) on KRAS and TP53 mutant CRC cell models. METHODS: We performed an experimental in vitro study utilizing lipofection to transfect KRAS and TP53 mutant CRC cell models (HCT 116 and HT-29 respectively) with E6/E7 oncoproteins of HPV types 16 and 18 individually and in combination. Subsequently, we assessed their synergistic effect on cell proliferation, invasion, migration, and survival. In addition, we also compared the protein expression patterns of key epithelial-mesenchymal transition (EMT) biomarkers like E-cadherin, fascin, and vimentin among transfected, co-transfected, and wild-type cells. RESULTS: We found that the co-expression of E6/E7 of HPV types 16 and 18 enhanced cell proliferation, invasion, migration, and survival in both cell models. Interestingly, this was also accompanied by the deregulation of all three EMT biomarkers, E-cadherin, fascin, and vimentin. The synergistic effect of the viral oncoproteins in promoting cancer was more pronounced in TP53 mutant cells (HT-29) as compared to KRAS mutant cells (HCT 116). We also report that HPV type 18 can induce a greater and more sustained oncogenic outcome as compared to HPV type 16. CONCLUSION: Our data indicate that co-expression of the E6/E7 oncoproteins of HPV types 16 and 18 can enhance oncogenic processes in CRC, especially TP53 mutant CRC.
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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 | 0.000 | 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 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".