Abstract P5-14-07: Impact of time to treatment (TTT) on recurrence free survival in non metastatic invasive breast cancer

Microtubule targeting agents (MTAs) continue to be some of the most valuable drugs used to treat breast cancer. While decades of research have shown that these drugs cause mitotic arrest in cells by suppressing the dynamic instability of microtubules, recent evidence demonstrates that the ability of MTAs to disrupt microtubule-dependent transport of key signaling components, including proteins and microRNAs, in interphase cells likely contributes to their anticancer actions. TGF-β signaling is a driver of oncogenesis and epithelial-to-mesenchymal transition (EMT) that involves multiple protein trafficking and intracellular signaling events. Ligand mediated activation of the cell surface TGF-β receptors leads to downstream signaling in the canonical and the non-canonical pathways that collectively lead to the expression of proteins implicated in EMT, including Snail and Slug. Additionally, TGF-β type 1 receptor (TGF-βR1) undergoes constant cycling from the plasma membrane to the cytosol, a microtubule-dependent process. We tested the hypothesis that a short-term treatment of breast cancer cells with eribulin or 3 other clinically relevant MTAs would differentially disrupt interphase microtubules and alter the transport and downstream signaling of TGF-βR1. BT-549 cells were treated for 2 h with concentrations of MTAs that cause comparable disruption of the interphase microtubule network; 100 nM was used for the destabilizers, eribulin or vinorelbine and 1 µM was used for ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research