Abstract P1-07-12: Kaiso is a novel regulator of epithelial-to-mesenchymal transition in triple negative breast cancer cells
Bibliographic record
Abstract
Abstract Introduction: Breast cancer (BC) is the most frequent form of female cancer and a principal cause of female deaths worldwide. Most BC deaths are attributed to tumor metastasis to vital organs, and many studies have proposed a role for epithelial-to-mesenchymal transition (EMT) in BC metastasis especially the Triple Negative BC (TNBC) subtype. This theory is further strengthened by the observation that many triple-negative tumors display low E-cadherin expression, which is a hallmark of EMT. The TNBC subtype lack expression of the estrogen-receptor (ER), progesterone-receptor (PR) and human epidermal growth factor receptor-2, HER2. These tumors are highly aggressive with limited treatment options or targeted-therapies, and consequently TNBC patients have poor outcomes. Recently, increased nuclear expression of the transcription factor Kaiso was significantly correlated with high grade, BRCA1-related and basal/TNBCs. Kaiso is a novel transcription factor that we originally identified as a binding partner of p120-catenin (p120), a Src Kinase substrate and regulator of E-cadherin stability and turnover. Rationale and Research Objective: Though not much is known about the function of Kaiso in breast tumor progression and metastasis, Kaiso has been implicated in regulating E-cadherin expression, which raised the possibility that Kaiso might play a role in EMT. Thus we sought to elucidate the role of Kaiso in EMT and TNBC metastasis. Results: To achieve this goal, we created a stable Kaiso-depleted TNBC cell line (MDA-MB-231) to analyze the consequences of Kaiso-depletion on features attributed to metastasis, using immunoblot, wound healing and Matrigel invasion assays among other techniques. Interestingly, Kaiso-depletion led to reduced transcript and expression levels of the EMT markers Snail, Slug, ZEB1/2, TGFbRII, vimentin, and up-regulation of E-cadherin. Kaiso-depleted MDA-MB-231 cells also showed a gradual change in morphology from a mesenchymal to an epithelial phenotype referred to as mesenchymal to epithelial transition (MET). Loss of Kaiso further resulted in reduced cell motility and invasion. Ongoing studies seek to evaluate the effect of Kaiso-depletion on metastasis in vivo. Since there is evidence that the TGFβ signaling pathway drives EMT, and Kaiso-depletion resulted in reduced transcript levels of TGFβRII, future studies will determine if Kaiso plays a role in EMT/MET via promotion of the TGFβ signaling pathway. Overall Significance: Our study is the first to demonstrate a link between Kaiso and EMT/MET of TNBC cells and suggest that Kaiso may be a novel regulator of EMT in TNBC. Consequently, Kaiso might be useful as a therapeutic or prognostic tool in the treatment of TNBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-07-12.
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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) | 0.005 | 0.002 |
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".