Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment
Why this work is in the frame
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Bibliographic record
Abstract
Solid tumors are challenged with a hypoxic and nutrient-deprived microenvironment. Hence, hypoxic tumor cells coordinatively increase the expression of nutrient transporters and pH regulators to adapt and meet their bioenergetic and biosynthetic demands. Carbonic Anhydrase IX (CAIX) is a membrane-bound enzyme that plays a vital role in pH regulation in the tumor microenvironment (TME). Numerous studies have established the importance of CAIX in mediating tumor progression and metastasis. To understand the mechanism of CAIX in mediating tumor progression, we performed an unbiased proteomic screen to identify the potential interactors of CAIX in the TME using the proximity-dependent biotin identification (BioID) technique. In this review, we focus on the interactors from this BioID screen that are crucial for nutrient and metabolite transport in the TME. We discuss the role of transport metabolon comprising CAIX and bicarbonate transporters in regulating intra- and extracellular pH of the tumor. We also discuss the role of amino acid transporters that are high confidence interactors of CAIX, in optimizing favorable metabolic state for tumor progression, and give our perspective on the coordinative interplay of CAIX with the amino acid transporters in the hypoxic TME.
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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 | 0.000 |
| 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 it