Abstract IA09: Translational control of the tumor microenvironment
Bibliographic record
Abstract
Abstract Translational control has emerged as a critical determinant in tumorigenesis. The mRNA cap-binding protein eIF4E is an oncoprotein that plays an important role in cancer initiation and progression. We recently demonstrated that eIF4E phosphorylation on serine 209 by the Map Kinase Integrating Kinases (MNK1/2) promotes epithelial to mesenchymal transition, invasion and metastasis. We recently discovered a critical importance of eIF4E phosphorylation in the tumor microenvironment (TME) for the metastatic process. To investigate the role of eIF4E phosphorylation in the TME, we utilized a syngeneic model in which a murine mammary tumor cell line (66cl4) was orthotopically injected into mice bearing the non-phosphorylatable eIF4E ^S209A mutation and their WT counterparts. Tumor growth was monitored by caliper measurements, and tissues were collected for histological assessment and immunohistochemistry. The onset of tumor formation was significantly delayed in eIF4E ^S209A mice. However, established tumors showed no differences in growth, proliferation, apoptosis, vascularization or immune infiltration. Strikingly, eIF4E ^S209A mice were nearly completely resistant to the formation of lung metastases from primary mammary tumors. Metastatic potential in this model was correlated with neutrophil accumulation in the spleen, blood and lungs of WT mice, which was significantly reduced in eIF4E ^S209A mice. Furthermore, treatment of tumor-bearing WT mice with an inhibitor of MNK1/2 significantly reduced lung metastasis without affecting primary tumor growth. Considering that eIF4E phosphorylation in both the TME and cancer cells promotes metastasis, our findings support the development of MNK inhibitors for metastasis prevention. Citation Format: Nathaniel Robichaud, Qianyu Guo, Sonia del Rincon, Wilson H. Miller, Peter Siegel, Brian Hsu, Nahum Sonenberg. Translational control of the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr IA09.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".