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.

HNRNPK is retained in the cytoplasm by Keratin 19 to stabilize target mRNAs

“…This suggested that K19 has little to no effect on the mechanism of nucleic acid recognition by HNRNPK and that changes in HNRNPK gene regulatory activity were most likely due to changes in its localization. Indeed, keratins regulate the localization of proteins in the cytoplasm to impact cellular and physiological processes including cell cycle, translation, cell-cell adhesion (25,(34)(35)(36). Our data show that in the presence of K19, HNRNPK increases the abundance of target mRNAs in the cytoplasm, very likely by increasing their stability and possibly through competition with other RBPs (37).…”