KCC3 activity contributes to the elongated spindle‐shaped morphology of invasive gliomas
Bibliographic record
Abstract
Salt and obligatory water efflux across the cell membrane contributes to the elongated spindle‐shaped morphology commonly observed with invasive glioma cells. Immunofluorescent localization of the K‐Cl cotransporter isoform 3 (KCC3) to migrating extensions of rat glioblastoma (C6) cells suggests that its activity may be responsible for this salt and water efflux and thus play a significant role in the motility of these tumor cells through the tight extracellular spaces in the brain. Unfortunately, the ubiquitous expression of KCC3 in other tissues makes it an unlikely target for novel anti‐cancer therapeutics. K‐Cl cotransporters are activated by dephosphorylation of specific threonine residues located in their intracellular carboxy‐terminal domain. Western blot analysis of protein lysates from several different immortalized tumor cell lines demonstrates an abundant expression of protein phosphatase 1 (PP1). In a series of wound healing experiments, Calyculin A inhibition of PP1 activity prevented C6 cells from moving into the wound area without varying the viability of cells outside the wound area. Furthermore, C6 cells incubated with Calyculin A no longer exhibited an elongated spindle‐shape, but rather a truncated rounder form. Interestingly, this same truncated form was observed in C6 cells where KCC3 was stably knocked down with short hairpin RNA, confirming that KCC3 activity plays a role in maintaining the elongated spindle‐shape associated with invasive motility. These results suggest that targeting the regulatory pathway of K‐Cl cotransport in glioma cells might be an effective way of slowing the spread of these malignant brain tumors. Support or Funding Information Supported by a Special Projects Grant from the University of Saskatchewan College of Medicine to Kenneth B. Gagnon.
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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 | 0.001 |
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".