Analysis of the effects of aryl hydrocarbon receptor expression on cancer cell invasion<i>via</i>three-dimensional microfluidic invasion assays
Bibliographic record
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds to xenobiotics and activates expression of response elements to metabolize these compounds. The AHR pathway has been associated with a long list of diseases including cancer; however, it is debated whether AHR is tumorigenic or tumour-inhibiting. In particular, there are contradictory reports in the literature regarding the effects of AHR expression level on metastatic breast cancer. Here we used a 3D invasion assay called cell invasion in digital microfluidic microgel systems (CIMMS) to study the effect of AHR expression on invasion. In this study, MDA-MB-231 cells with stable knockout of AHR (AHRko) showed enhanced invasive characteristics and reduced proliferation, and cells with transient overexpression of AHR showed reduced invasiveness. Overexpression of AHR with a mutation in the DNA binding domain showed no difference in invasiveness compared to control, which suggests that the changes in invasiveness are related to the expression of AHR. CIMMS also allowed for extraction of sub-populations of invaded cells for RNA sequencing experiments. A comparison of the transcriptomes of invaded subpopulations of wild-type and AHRko cells identified 1809 genes that were differentially expressed, with enriched pathways including cell cycle, proliferation, survival, immunoproteasome activation, and activation of matrix metalloproteases. In sum, the data reported here for MDA-MB-231 cells suggests some new interpretations of the discrepancy in the literature on the role of AHR in breast cancer. We propose that the unique combination of functional discrimination with transcriptome profiling provided by CIMMS will be valuable for a wide range of mechanistic invasion-biology studies in the future.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".