Abstract 4464: CPEB-2 is a tumor-suppressor gene in human breast cancer
Bibliographic record
Abstract
Abstract We found that expression of cyclooxygenase (COX)-2 promotes breast cancer progression by multiple mechanisms, including stimulation of cancer cell proliferation, migration, invasiveness, epithelial-to-mesenchymal transition (EMT), angiogenesis, lymphangiogenesis and induction of stem-like cells (SLC). Through combined gene expression and microRNA microarray analyses of COX-2-transfected MCF-7 cells, we identified two oncogenic miRNAs, miR-526b and miR-655, up-regulated by COX-2. They collectively target 13 tumour suppressor-like genes down-regulated by COX-2, of which Cytoplasmic Polyadenylation Element-Binding Protein -2 (CPEB-2) was the single common target, whose function is unclear in breast cancer. CPEB-2 is known to downregulate mesenchymal transcription factor TWIST1 and translation of HIF1α. CPEB-2 has multiple isoforms (A-F), of which a high B: A isoform ratio was reported to confer anoikis-resistance, a metastatic phenotype, in breast cancer cells. We found that CPEB-2 expression was inversely correlated with COX-2 or the microRNAs miR-526b and miR-655 in breast cancer cell lines; it was very high in a non-tumorigenic mammary epithelial cell line MCF10A.To define its functional roles we knocked out CPEB-2 in MCF10A cells by CRISPR/Cas9-double nickase approach. CPEB-2-KO cells exhibited oncogenic phenotypes in vitro: increased proliferation, migration, invasion, EMT phenotype (decreased E-Cadherin, increased Vimentin, N-cadherin, SNAI1, and ZEB1) and SLC properties (increased spheroid formation and SLC-linked markers). P53 protein was found to be a novel translationally- regulated target of CPEB-2. CPEB-2KO cells, but not wild-type cells, produced lung colonies upon intravenous injection and orthotopic tumors (identified by HLA staining) upon implantation at mammary sites in NOD/SCID/IL2Rϒ-null mice. In human breast cancer tissues, compared to non-tumour breast tissues, isoform A/E of CPEB2 revealed a lower expression in HER2+ breast cancer samples, suggesting that CPEB-2A/E are the tumour-suppressor isoforms. These findings demonstrate that CPEB-2 is a tumour suppressor gene in breast cancer. (Supported by the OICR and the NSERC) Citation Format: Peeyush K. Lala, Joshua Tordjman, Mehdi Amiri, Asma Hasan, David Hess, Mousumi Majumder. CPEB-2 is a tumor-suppressor gene in human breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4464.
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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 | 0.001 | 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) | 0.004 | 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".