Abstract A61: Cell cycle regulated centrosome orientation during directed migration requires Aurora Kinase A

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 phosphoryl...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research