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.
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 | 0.000 | 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) | 0.002 | 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".