Abstract 2008: CENP-E kinesin facilitates chemokine ligand CCL18 translocation to promote migration in triple negative breast cancer

Abstract

Abstract Our research is focused on the molecular mechanisms responsible for enhanced cellular proliferation and migration as it relates to triple negative breast cancer (TNBC). Advances in visualization techniques and technologies work to provide an in-depth view of various cellular mechanisms, allowing us to capture molecular level protein-protein interactions previously unknown. There are more than 40 kinesin motor proteins found within the spindle assembly checkpoint, classified into 14 families, which each play essential roles in microtubule-dependent intracellular trafficking. This assembly is a critical component to the cell cycle control complex that acts during mitosis to prevent chromosome missegregation and aneuploidy. Centromere associated protein E (CENP-E) is a kinesin motor protein that shows aberrant overexpression in TNBC which facilitates exponential cell growth and eventual metastasis that occurs in TNBC. Growing awareness through scientific discoveries sheds light on the fact that it is a rare occurrence for biological functions to be attributed to a single mutated macromolecule. Most physiological processes arise from a complex orchestration of cellular events occurring between multiple molecules acting in concert. The nature of protein-protein transactions that drive gene activation appear to be dynamic in TNBC cells thus enabling uncontrolled proliferation. We believe that a pleiotropic network of small molecules may be working cooperatively with CENP-E to facilitate the exponential cell growth and eventual metastasis that occurs in TNBC cells. Currently, we are carrying out spectral imaging and biophysical force measurements to delineate CCL18-elicited cell mechanics and breast cancer metastasis. To address this, we have incorporated syntelin, a small inhibitory molecule targeted to CENP-E in an effort to analyze the resultant effect it has on this network of proteins we believe may be involved in the CENP-E signaling cascade. Taken together, these results indicate that syntelin may comprise a novel targeted chemotherapeutic intervention for TNBC. Citation Format: McKay M. Mullen. CENP-E kinesin facilitates chemokine ligand CCL18 translocation to promote migration in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2008.