Ewing tumor cells grown as anchorage independent multicellular spheroids suppress anoikis through an E-cadherin dependent cell survival pathway.
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 5637 Most normal mammalian cells cannot survive if they become detached from the extracellular matrix (ECM), instead undergoing detached-induced programmed cell death or anoikis. However, a major hallmark of transformed cells is that they can survive under anchorage independent conditions including suspension cultures. During metastatic spread, tumor cells detach from primary sites and must then survive under anchorage independent conditions before establishing ECM contacts at distant metastatic sites. Understanding how these cells suppress anoikis is key to developing therapeutic strategies targeting micrometastases in the circulation or the bone marrow. To investigate the biological mechanisms underlying suppression of anoikis we analyzed the consequences of transferring Ewing tumor cell lines from conventional monolayers to anchorage independent cultures on agar-coated plates. This resulted in the rapid formation of multicellular tumor spheroids while single cells underwent cell death. While integrins mediated attachment of monolayer cells to plastic, spheroid formation was associated with E-cadherin mediated cell-cell adhesion. Ewing tumor spheroids showed a dramatic increase in chemoresistance to a wide spectrum of anti-neoplastic agents compared to monolayer cultures of the same cell lines, and this was reversed by blocking E-cadherin cell-cell contacts. Spheroid cells demonstrated increased activation of the Rac1 or Cdc42 GTPases, and dominant negative Rac1/cdc42 blocked spheroid cell survival. In addition, several receptor tyrosine kinases such as ErbB4, NTRK3, IGF1R and PDGFRβ became activated in spheroid cells. Of these, ErbB4 activation was found to be particularly high in Ewing tumor spheroids. These results indicate that anchorage independent Ewing tumor cells suppress anoikis through a pathway involving E-cadherin cell-cell adhesion, Rho GTPase activation, and stimulation of receptor tyrosine kinases.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".