Transcriptome Analysis Reveals Vimentin-Induced Disruption of Cell–Cell Associations Augments Breast Cancer Cell Migration
Saima Usman,
Ahmad Jamal,
Antesar Bushaala,
Naushin H. Waseem,
Hebah Al-Dehlawi,
William Andrew Yeudall,
Muy-Teck Teh,
Hemanth Tummala,
Ahmad Waseem
Affiliations
Saima Usman
Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Newark Street, London E1 2AT, UK
Ahmad Jamal
Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Newark Street, London E1 2AT, UK
Antesar Bushaala
Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Newark Street, London E1 2AT, UK
Naushin H. Waseem
St Bartholomew’s Hospital, Barts NHS Trust, King George V Building, 5th Floor, London EC1A 7BE, UK
Hebah Al-Dehlawi
Department of Oral Diagnostic Sciences, Division of Oral Pathology and Medicine, Faculty of Dentistry, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
William Andrew Yeudall
Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA 30912, USA
Muy-Teck Teh
Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Newark Street, London E1 2AT, UK
Hemanth Tummala
Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AT, UK
Ahmad Waseem
Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Newark Street, London E1 2AT, UK
In advanced metastatic cancers with reduced patient survival and poor prognosis, expression of vimentin, a type III intermediate filament protein is frequently observed. Vimentin appears to suppress epithelial characteristics and augments cell migration but the molecular basis for these changes is not well understood. Here, we have ectopically expressed vimentin in MCF-7 and investigated its genomic and functional implications. Vimentin changed the cell shape by decreasing major axis, major axis angle and increased cell migration, without affecting proliferation. Vimentin downregulated major keratin genes KRT8, KRT18 and KRT19. Transcriptome-coupled GO and KEGG analyses revealed that vimentin-affected genes were linked to either cell–cell/cell-ECM or cell cycle/proliferation specific pathways. Using shRNA mediated knockdown of vimentin in two cell types; MCF-7FV (ectopically expressing) and MDA-MB-231 (endogenously expressing), we identified a vimentin-specific signature consisting of 13 protein encoding genes (CDH5, AXL, PTPRM, TGFBI, CDH10, NES, E2F1, FOXM1, CDC45, FSD1, BCL2, KIF26A and WISP2) and two long non-coding RNAs, LINC00052 and C15ORF9-AS1. CDH5, an endothelial cadherin, which mediates cell–cell junctions, was the most downregulated protein encoding gene. Interestingly, downregulation of CDH5 by shRNA significantly increased cell migration confirming our RNA-Seq data. Furthermore, presence of vimentin altered the lamin expression in MCF-7. Collectively, we demonstrate, for the first time, that vimentin in breast cancer cells could change nuclear architecture by affecting lamin expression, which downregulates genes maintaining cell–cell junctions resulting in increased cell migration.
