Oxidative stress induces the acquisition of cancer stem-like phenotype in breast cancer detectable by using a Sox2 regulatory region-2 (SRR2) reporter
Bibliographic record
Abstract
// Keshav Gopal 1,* , Nidhi Gupta 1,* , Haifeng Zhang 1 , Abdulraheem Alshareef 1 , Hind Alqahtani 1 , Gilbert Bigras 1 , Jamie Lewis 2 , Donna Douglas 2 , Norman Kneteman 2 , Afsaneh Lavasanifar 3,4 and Raymond Lai 1,3,4,5 1 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada 2 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada 3 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada 4 Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, Canada 5 Department of Oncology, University of Alberta, Edmonton, Alberta, Canada * These two authors share the first authorship Correspondence to: Raymond Lai, email: // Keywords : breast cancer, Sox2, H 2 O 2 , acquisition of stemness, plasticity Received : June 08, 2015 Accepted : November 14, 2015 Published : December 16, 2015 Abstract We have previously identified a novel intra-tumoral dichotomy in breast cancer based on the differential responsiveness to a Sox2 reporter (SRR2), with cells responsive to SRR2 (RR) being more stem-like than unresponsive cells (RU). Here, we report that RR cells derived from MCF7 and ZR751 displayed a higher tolerance to oxidative stress than their RU counterparts, supporting the concept that the RR phenotype correlates with cancer stemness. Sox2 is directly implicated in this differential H 2 O 2 tolerance, since siRNA knockdown of Sox2 in RR cells leveled this difference. Interestingly, H 2 O 2 converted a proportion of RU cells into RR cells, as evidenced by their expression of luciferase and GFP , markers of SRR2 activity. Compared to RU cells, converted RR cells showed a significant increase in mammosphere formation and tolerance to H 2 O 2 . Converted RR cells also adopted the biochemical features of RR cells, as evidenced by their substantial increase in Sox2-SRR2 binding and the expression of 3 signature genes of RR cells ( CD133, GPR49 and MUC15 ). Lastly, the H 2 O 2 -induced RU/RR conversion was detectable in a SCID mouse xenograft model and primary tumor cells. To conclude, the H 2 O 2 -induced RU/RR conversion has provided a novel model to study the acquisition of cancer stemness and plasticity.
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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) | 0.000 | 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".