Abstract 3502: Chemoproteomics provide insights into cell surface reprogramming during KRAS-mediated transformation
Bibliographic record
Abstract
Abstract KRAS is among the most frequently mutated genes driving human cancers, including ~45% of colorectal cancers (CRC). Despite decades of research, mutant KRAS is considered undruggable, and is frequently associated with resistance to chemotherapy and other targeted therapies. While the effect of mutant KRAS on regulating intracellular signaling events is well studied, much less is known about its impact on the cell surface proteome (surfaceome), which constitutes the predominant therapeutic target for FDA-approved drugs. To study the cell surfaceome, we optimized a chemoproteomics approach that selectively isolates cell surface proteins and allows their relative quantification using mass spectrometry. When comparing normal intestinal cells to their counterparts expressing oncogenic KRAS (G12V), we identified 104 (~13%) and 170 (~22%) cell surface proteins that were significantly upregulated or downregulated, respectively, in KRAS-transformed cells. Overall, a myriad of proteins, including receptors, solute carriers, adhesion molecules, etc., were modulated by mutant KRAS, and their potential roles in KRAS-mediated transformation are currently being studied. We also found that most of the cell surface proteins were altered in response to transcriptional changes induced by KRAS signaling, and due to increased global endocytosis in KRAS-mutated cells. Our study suggests potential cell surface proteins that could be targeted in KRAS-mutant cells, which will be verified in subsequent studies using human CRC models. Our work helps assemble a global view of how oncogenic KRAS alters the spatial distribution of several cell surface proteins, and thereby potentially impacts tumor functions and therapeutic response. Citation Format: Neethi Nandagopal, Léo Aubert, Sami Nourreddine, Geneviève Lavoie, Philippe Roux. Chemoproteomics provide insights into cell surface reprogramming during KRAS-mediated transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3502.
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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) | 0.002 | 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".