Abstract P1-05-22: Breast cancer cells that undergo an Epithelial-to-Mesenchymal transition co-opt LPP, a regulator of mesenchymal cell migration and invasion.
Bibliographic record
Abstract
Abstract Transforming Growth Factor β (TGFβ) promotes breast cancer cell metastasis to multiple sites, including the bone and lungs. TGFβ is a strong inducer of Epithelial-to-Mesenchymal transitions (EMT) and breast cancers that exhibit features of an EMT acquire stem cell-like characteristics, are highly aggressive, are resistant to therapy and are refractory to tumor suppressive processes. While TGFβ itself is non-oncogenic, it is a potent modifier of the malignant phenotype in breast cancer and is capable of enhancing the migration, invasion and metastasis of ErbB2 expressing breast cancer cells. We have identified Lipoma Preferred Partner (LPP) as an indispensable regulator of TGFβ-induced migration and invasion of ErbB2 expressing breast cancer cells. LPP is ubiquitously expressed in smooth muscle cells where it mediates cell adhesion, migration and the formation of lamellipodial extensions. We hypothesize that breast cancer cells capable of undergoing an EMT can utilize novel mediators that are engaged in promoting the migration and invasion of mesenchymal cells. We propose that LPP is one such example, which promotes the migration and invasion of ErbB2 expressing breast cancer cells that have undergone a TGFβ-induced EMT. We demonstrate that ErbB2 expressing breast cancer cells display significant increases in cell migration and invasion upon TGFβ stimulation, and such responses are dependent on LPP expression. We show that LPP re-localizes to focal adhesion complexes following TGFβ-induced EMT and it is a critical determinant in focal adhesion turnover. Furthermore, we determined that LPP targeting to focal adhesions through its LIM1 domain requires the cooperation of ErbB2 and TGFβ signaling pathways. Finally, we demonstrate that LPP promotes TGFβ-induced migration and invasion of ErbB2 expressing breast cancer cells through recruitment of α-Actinin, an actin cross-linking protein. Overall, we have identified LPP as a novel mediator that integrates TGFβ and ErbB2 signaling to promote the migration and invasion of breast cancer cells that undergo an EMT. Our data reveal that breast cancer cells, which can transition from an epithelial to mesenchymal phenotype, can engage a regulator of mesenchymal cell migration and invasion. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-22.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 |
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 teacher head, 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".