Downregulation of FHOD1 Inhibits Metastatic Potential in A549 Cells

Marta Hałas-Wiśniewska, Magdalena Izdebska, Wioletta Zielińska, Alina Grzanka Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Bydgoszcz 85-092, PolandCorrespondence: Marta Hałas-WiśniewskaDepartment of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, 24 Karłowicza Street, Bydgoszcz 85-092, PolandTel +48525853725Fax +48525853734Email mhalas@cm.umk.plPurpose: Metastasis remains a serious clinical problem in which epithelial-to-mesenchymal transition is strictly involved. The change of cell phenotype is closely related to the dynamics of the cytoskeleton. Regarding the great interest in microfilaments, the manipulation of ABPs (actin-binding proteins) appears to be an interesting treatment strategy.Material: The research material was the highly aggressive A549 cells with FHOD1 (F FH1/FH2 domain-containing protein 1) downregulation. The metastatic potential of the cells and the sensitivity to treatment with alkaloids (piperlongumine, sanguinarine) were analyzed.Results: In comparison to A549 cells with naïve expression of FHOD1, those after manipulation were characterized by a reduced migratory potential. The obtained results were associated with microfilaments and vimentin reorganization induced by the manipulation of FHOD1 together with alkaloids treatment. The result was also an increase in the percentage of late apoptotic cells.Conclusion: Downregulation of FHOD1 induced reorganization of microfilament network followed by the reduction in the metastatic potential of the A549 cells, as well as their sensitization to selected compounds. The presented results and the analysis of clinical data indicate the possibility of transferring research from the basic level to in vivo models in the context of manipulation of ABPs as a new therapeutic target in oncology.Keywords: FHOD1, lung cancer, F-actin, migration, A549