Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

Abstract

A cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. Using KRT19 knockout (KO) cells and cells where K19 expression was rescued, we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion of MCF7 cells. A loss of K19 resulted in a lower level of plakoglobin and internalization of E-cadherin in early and recycling endosomes. Inhibiting internalization restored cell-cell adhesion of KRT19 KO cells, suggesting E-cadherin internalization contributes to defective adhesion. Ultimately, while K19 inhibited cell migration, it was required for cells to form colonies in suspension. Our results suggest that K19 stabilizes E-cadherin complexes at the cell membrane to maintain cell-cell adhesion which inhibits cell migration but provides growth and survival advantages for circulating tumor cells. These findings provide context-dependent roles of K19 during metastasis.