Superoxide Dismutase 1 Regulation of CXCR4‐Mediated Signaling in Prostate Cancer Cells is Dependent on Cellular Oxidative State
Bibliographic record
Abstract
CXCL12, acting via its G protein‐coupled receptor CXCR4, is a chemoattractant for a broad range of cell types, including several types of cancer cells. Indeed, elevated expression of CXCR4, and its ligand CXCL12 play important roles in promoting cancer metastasis. Cancer cells have the potential for rapid and unlimited growth in a restricted blood supply; oxidative stress is a common feature of several tumors. Superoxide dismutase (SOD) is a critical enzyme responsible for regulation of superoxide radicals. Recent studies have reported enhanced expression of SOD may increase the aggressive and invasive potential of malignant cells in some cancers. Here, we report a direct interaction between SOD1 and CXCR4. Given the important roles of these two proteins in cancer progression and metastasis, we characterized the effects of SOD1 on CXCR4 signal transduction. We showed that SOD1 interacts directly with the first intracellular loop of CXCR4. We demonstrated that CXCL12/CXCR4‐mediated modulation of ERK, AKT, apoptosis and cell migration in prostate cancer cells is different under normal versus hypoxic conditions when SOD1 is present. Finally, we identified a potential regulatory mechanism by which SOD1 directly interferes with CXCR4 function, regulating G protein coupling to CXCR4, and promoting a relative switch in G protein coupling from G i to G q depending on environmental conditions. This study highlights a potential new regulatory mechanism by which a sensor of the oxidative environment can directly regulate signal transduction of a receptor involved in cancer cell survival and migration. Supported the Dalhousie Medical Research Foundation and Natural Sciences and Engineering Research Council of Canada.
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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 | 0.000 |
| 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 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".