Rho/ROCK‐dependent pseudopodial protrusion and cellular blebbing are regulated by p38 MAPK in tumour cells exhibiting autocrine c‐Met activation
Bibliographic record
Abstract
BACKGROUND INFORMATION: The c-Met-dependent, beta-actin-rich, blebbed pseudopodia of MSV-MDCK-INV (invasive Moloney-sarcoma-virus-transformed Madin-Darby canine kidney) cells are induced by Rho/ROCK (Rho kinase) activation, and are morphologically distinct from flat extended lamellipodia. RESULTS: Microtubules were shown to extend to these actin-rich pseudopodial domains, and microtubule depolymerization by nocodazole treatment resulted in progressive cellular blebbing, initiating in the pseudopodial domains and resulting in transient cellular rounding and blebbing after 30 min. The blebbing response was dependent on autocrine HGF (hepatocyte growth factor) activation of c-Met and prevented by inhibition of RhoA, ROCK and p38 MAPK (p38 mitogen-activated protein kinase), but not ERK (extracellular-signal-regulated kinase) or PI3K (phosphoinositide 3-kinase). Phospho-p38 MAPK was present in pseudopodia, localizing activation of this signalling pathway to this protrusive membrane structure. In serum-starved cells, LPA (lysophosphatidic acid) activation of RhoA induced p38 MAPK-dependent pseudopodial protrusions, and inhibition of p38 MAPK prevented pseudopodial protrusion and displacement of MSV-MDCK-INV cells. MSV-MDCK-INV cells exhibited intermittent blebbing and rounding, which may represent an integral part of their motile behaviour. CONCLUSIONS: The localized activation of an autocrine HGF/c-Met loop regulates Rho/ROCK activation of p38 MAPK signalling to stimulate both membrane blebbing and pseudopod formation.
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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) | 0.002 | 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".