Abstract 535A: The tyrosine kinase Src co-operates with the ERM family member ezrin to promote Met activation and ECM degradation in a breast epithelial cell model
Bibliographic record
Abstract
Abstract Over-expression and aberrant activation of the Met proto-oncogene frequently occurs in invasive breast cancer, and is linked with poor patient prognosis. We and others have shown that the tyrosine kinase Src mediates cell-adhesion dependent activation of Met in the absence of ligand (JCB 107:1168-81, 2009). We have also shown that Src acts co-operatively with the membrane cytoskeletal crosslinker ezrin to disrupt cell-cell contacts, and to increase cell spreading and scattering, all characteristics of epithelial-to-mesenchymal transition (EMT) (JCB 92:16-28, 2004). We therefore examined the role of Src and ezrin in Met activation and invasion of breast epithelial cells. As a model, we used the HC11 breast epithelial cell line expressing various combinations of activated Src and ezrin mutants, as well as a dominant negative ezrin mutant. In contrast to activated Src, which promotes the phosphorylation and hence activation of Met and cell spreading, activated ezrin alone induces the formation of numerous filopodia-like structures, but not Met phosphorylation or cell spreading. Co-activation of Src and ezrin produces a combination of both cell spreading and filopodia-like structures, and strongly increases Met phosphorylation over levels resulting from activated Src alone. Interestingly, Src/ezrin co-operativity dramatically increases tyrosine-phosphorylation of cortactin and MMP2 expression, resulting in the formation of invadopodia and extracellular matrix degradation, a hallmark feature of invading cancer cells. However expression of a dominant negative ezrin domain (aa1-309) abolishes Src and ezrin-induced morphological phenotypes, as well as Src-dependent Met phosphorylation and invadopodia formation, suggesting an important requirement for ezrin in these processes. These findings implicate the Src/ezrin axis in regulating adhesion-dependent Met activation and invadopodia formation, and may provide important clues toward treatment strategies for invasive breast tumors which exploit this signaling pathway (Supported by CBCRA and CIHR). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 535A.
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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".