Immunofluorescent staining showing loss of β-catenin or E-cadherin (green) at the cell membrane in breast cancer cells expressing an empty vector or CK5 (red).
Cytokeratin regulation of breast cancer cells
Cytokeratins (CKs) are the intermediate filament proteins of epithelial cells that form a dynamic cytoskeleton that provides mechanical stability and protects the cell from stress. While most ER+ breast cancers express “luminal” CKs 8, 18, and 19, some tumors express “basal” CKs 5 and 17 which are associated with worse outcomes. We are investigating how basal CKs remodel breast cancer cells and influence behavior such as motility, invasion and metastasis. We discovered that basal CKs remodel cell junctions and influence transcription through crosstalk with β-catenin and Wnt signaling and are further pursuing these mechanisms as well as how the ER+ and ER- cells cross-communicate with each other and the tumor microenvironment. The goal is to better understand how basal CKs maintain the CSC phenotype and discover creative ways to disrupt this.