Abstract 2093: LPP promotes ErbB2 overexpressing breast cancer cell migration, invasion and metastasis
Bibliographic record
Abstract
Abstract Metastatic breast cancer remains a major hurdle to the successful treatment of this disease. Overexpression of the HER2/ErbB2 receptor tyrosine kinase in breast cancer is associated with metastatic disease and correlates with poor patient prognosis. Growing evidence demonstrates that TGFβ can potentiate ErbB2 signaling to enhance the invasive and metastatic behavior of breast cancer cells. Nonetheless, the mechanisms underlying the synergy between TGFβ and ErbB2 signaling pathways remain to be elucidated. We previously identified Lipoma Preferred Partner (LPP) as an indispensable mediator of TGFβ-induced migration, invasion and focal adhesion turnover of ErbB2-expressing breast cancer cells. Furthermore, we established domains within LPP that are required for its localization to focal adhesions and for its interaction with α-Actinin, an actin cross-linking protein, to promote cell migration and invasion. Herein, we examine the requirement of LPP in tumorigenesis and metastasis formation. We observe that LPP is dispensable for primary tumor growth. Nonetheless, the loss of LPP leads to decrease in spontaneous lung metastasis formation of ErbB2-expressing breast cancer cells injected into the mammary fat pads of mice. Furthermore, we observe that LPP is a critical determinant for efficient dissemination of breast cancer cells. We show that shRNA-mediated reduction of LPP significantly impairs pulmonary metastasis formation in experimental metastasis tail vein assay. Overall, we have identified LPP as a novel mediator that integrates TGFβ and ErbB2 signaling to promote the migration, invasion and metastasis of breast cancer cells. We identify LPP as a pro-metastatic mediator of ErbB2 overexpressing breast cancer cells and a potential new biomarker of metastatic breast cancer. Citation Format: Elaine Ngan, Peter M. Siegel. LPP promotes ErbB2 overexpressing breast cancer cell migration, invasion and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2093. doi:10.1158/1538-7445.AM2014-2093
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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) | 0.004 | 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".