Abstract A61: Cell cycle regulated centrosome orientation during directed migration requires Aurora Kinase A
Bibliographic record
Abstract
Abstract Cell cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells. Here we report a strong correlation between cell cycle progression into G2 phase and an increased migratory velocity for non-malignant, immortalized mammary epithelia nMuMG (Mus musculus mammary gland) cells, or malignant cervical carcinoma HeLa cells, expressing a fluorescent ubiquitin cell cycle indicator and quantified in wound closure assays with high content multi-parameter live cell imaging. Cells at the wound edge exhibited elevated microtubule nucleation capacity at centrosomes, and a reduction of this capacity through inhibition of aurora kinase A was sufficient to impair migration velocity without affecting cell cycle dynamics. In migratory cells, active aurora kinase A at the centrosome correlated with nucleation capacity. In clinically annotated mammary carcinoma tissues (n=3,992), aurora kinase A activity, as assessed by the abundance of phosphorylated-RHAMM (Receptor for Hyaluronan Mediated Motility) was a significant predictor of breast cancer specific survival and relapse free survival in patients with estrogen receptor negative breast cancer (n= 941), triple negative phenotype breast cancer (n= 538) or basal-like subtype breast cancer (n= 293), but not in those patients with estrogen receptor positive breast cancer (n= 2,218). In estrogen receptor negative tumors from patients that received no adjuvant systemic therapy (n= 453), the levels of phosphorylated-RHAMM associated with the presence of distal nodal metastasis and predicted a subset of patients at high risk of recurrence. Together, these data identify aurora kinase A activity as a regulatory pathway that intersects cell cycle progression and cell migration, with potential to influence the metastasis of estrogen receptor negative breast tumors and patient survival. Citation Format: Tony LH Chu, Jennifer Won, Oksana Nemirovsky, Abbas Fotovati, Torsten Nielsen, Christopher A Maxwell. Cell cycle regulated centrosome orientation during directed migration requires Aurora Kinase A. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A61.
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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) | 0.001 | 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 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".