Abstract A236: The orphan G-protein coupled receptor GPR161 is an oncogene in triple negative breast cancer.
Bibliographic record
Abstract
Abstract Triple negative breast cancer (TNBC) accounts for 20% of breast cancer in women and lacks an effective targeted therapy. Therefore, finding common vulnerabilities in these tumors represents an opportunity for more effective treatment. Recent large-scale analyses of hundreds of tumor samples have provided a deluge of information on the genetic changes occurring during tumorigenesis. However, determining which changes drive tumor initiation and progression, and which are bystanders remains a difficult biological problem. Utilizing this genomic information we have discovered that the orphan G-protein coupled receptor (GPCR) GPR161 is overexpressed specifically in TNBC. TNBC patients expressing higher levels of GPR161 have an increased probability of disease relapse. Overexpression of GPR161 in human non-transformed mammary epithelial cells increases cell proliferation and multiacinar structure formation in three-dimensional (3D) culture through activation of mTORC1 signaling. Knockdown of GPR161 impairs proliferation of a human basal breast cancer cell line. Furthermore, GPR161 expression induces cell migration and invasion of cells in 3D culture. This is accompanied by disrupted cell adhesion and intracellular accumulation of E-cadherin. Cells overexpressing GPR161 show a reduction in IQGAP1 phosphorylation, consistent with mTOR activation and E-cadherin disruption. Furthermore, we find GPR161 in a signaling complex with the scaffold proteins β-arrestin 2 and IQGAP1. These results suggest that GPR161 may provide prognostic value and serve as a potential drug target in TNBC. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A236. Citation Format: Michael E. Feigin, Bin Xue, Molly Hammell, Senthil K. Muthuswamy. The orphan G-protein coupled receptor GPR161 is an oncogene in triple negative breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A236.
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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 | 0.000 |
| 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".