The Actin Motor Protein Myosin 6 Contributes to Cell Migration and Expression of GIPC1 and Septins in Breast Cancer Cells

Magdalena Izdebska,1,* Wioletta Arendt,1,* Marta Hałas-Wiśniewska,1 Przemysław Zakrzewski,2 Robert Lenartowski,3,4 Marta Lenartowska3,4 1Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland; 2School of Cellular and Molecular Medicine, Faculty of Life Sciences, University of Bristol, University Walk, Bristol, UK; 3Department of Cellular and Molecular Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, Toruń, Poland; 4Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University in Toruń, Toruń, Poland*These authors contributed equally to this workCorrespondence: Magdalena Izdebska, Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 24 Karłowicza St, Bydgoszcz, 85-092, Poland, Tel +48 52 585 37 25, Email [email protected]: Breast cancer is highly metastatic. One protein that may participate in breast cancer cell migration is the actin motor protein myosin 6 (MYO6), which is likely regulated by the GIPC1 protein. Additionally, septins (SEPTs) appear to participate in breast cancer motility. Here, we investigated the effects of loss of MYO6 on cell morphology, migration, and expression of GIPC1, SEPT2, and SEPT7 in two breast cancer cell lines.Material and Methods: The research material consisted of two breast cancer cell lines, MCF-7 and MDA-MB-231, in which the level of MYO6 was reduced and the effect of knockdown on the migration potential and the expression of GIPC1, SEPT2 and SEPT7 was determined. The levels of these proteins were also analyzed in silico.Results: siRNA-mediated knock down of MYO6 altered the morphology of MCF-7 cells and reduced the expression of GIPC1 and SEPT7 in both MCF-7 and MDA-MB-231 cells. In in silico data, GIPC1, SEPT2, and SEPT7 were all overexpressed in breast cancer tissue samples from patients. Finally, MYO6 knock down impaired migration and adhesion in both MCF-7 and MDA-MB-231 cells.Conclusion: Our study substantiates that downregulation of MYO6 diminishes the migratory abilities of breast cancer cell lines with varying invasiveness. Furthermore, we have demonstrated that decreased MYO6 protein leads to reduced expression of GIPC1, SEPT2, and SEPT7 in breast cancer cells. These findings contribute to a more comprehensive understanding of the pathways influencing breast cancer cell migration, a critical aspect of metastasis.Keywords: MYO6, breast cancer, actin, migration, GIPC1, SEPT