Abstract 3796: Endophilin II promotes breast tumor progression and metastasis.
Bibliographic record
Abstract
Abstract Invadopodia are filamentous actin-based membrane protrusions with extracellular matrix (ECM) degrading activity that are implicated in tumor progression and metastasis. A key step in invadopodia formation involves the recruitment of the membrane type 1 matrix metalloprotease (MT1-MMP) to invadopodia precursors. Surface expression of MT1-MMP promotes ECM degradation and cell invasiveness, and this is dependent on Src kinase-induced phosphorylation and inhibition of endocytic proteins. In fibroblasts, MT1-MMP internalization was regulated by Endophilin II (Endo II), a widely expressed protein implicated in synaptic vesicle uncoating and recycling in neurons. Here, we tested the role of Endo II in invadopodia formation in basal-like breast cancer cells, and in tumor progression and metastasis in mice. High levels of Endo II expression were observed in basal breast cancer cell lines with high Src kinase and ECM-degrading activity. Immunohistochemistry staining also identified Endo II expression in primary breast tumors and lymph node metastases. To define the functions of Endo II, we achieved stable silencing of Endo II in two basal breast cancer cell lines (MDA-MB-231, HCC1806). Although Endo II was not required for uptake of receptors via clathrin-mediated endocytosis (EGFR, TfR), we observed a significant reduction in numbers of invadopodia and ECM degradation upon Endo II silencing. Consistent with invadopodia defects in vitro, Endo II silencing led to a significant reduction in tumor growth and metastases in mouse orthotopic tumor xenografts assays performed with both basal breast cancer cell models. This study provides novel insights into roles of Endo II as a positive regulator of invadopodia and basal breast cancer metastasis. Citation Format: Tomas Baldassarre, Jalna Meens, Andrew W. Craig. Endophilin II promotes breast tumor progression and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3796. doi:10.1158/1538-7445.AM2013-3796
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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) | 0.001 | 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) | 0.005 | 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".