Abstract 5051: Docosahexaenoic acid inhibits cancer cell invasion and migration by modifying focal adhesion complex structure and signaling

The extracellular matrix (ECM) is responsible for the regulation of many cellular processes, including survival, proliferation, migration and invasion. Cellular-ECM contact induces a coordinated process recruiting functional protein complexes, consisting of scaffold, adapter, linking and docking proteins, to form focal adhesion (FA) structures. Once formed, FA complexes then recruit signaling proteins to activate downstream cellular pathways. Aberrations in FA structure and signaling have shown to contribute to cancer initiation, progression and cellular motility. Studies investigating the molecular mechanisms accounting for FA structure and function in cancer cells have demonstrated unique growth behavior and migratory properties in vitro. While docosahexaenoic acid (DHA), an omega-3 PUFA, has been shown to inhibit growth of a number of cancer cell lines, the effects of DHA on FA dynamics and signaling have not been investigated. In the present study, we show that DHA induced changes in the morphological growth phenotype in cancer cell lines grown in Matrigel™. DHA treatment also inhibited planar cell movement (cell migration) and amoeboid motility (invasion) in breast and lung cancer cell lines. Associated with the observed morphological changes and inhibited growth, were changes in the expression of a number of proteins involved in the FA complex. Upon further characterization, cell line specific changes in protein expression levels and protein localization of FAK, e-cadherin, paxillin and vinculin were observed with DHA treatment, which suggests that DHA is modifying FA complex structure. Additionally, changes in the phosphorylation patterns of major signaling pathways associated with the FA complex, like EGFR, ERK and c-Myc, were also observed with DHA treatment. Overall, these results provide new insight into FA activation and signaling and demonstrate a new mechanism for DHA treatment in cancer. Citation Format: Michael Mouradian, Palvinder K. Bains, Ronald S. Pardini. Docosahexaenoic acid inhibits cancer cell invasion and migration by modifying focal adhesion complex structure and signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5051.