Products Cited in Publications Worldwide Characterizing the Role of K19 in Maintaining the Structural Integrity of Breast Cancer Cells

Characterizing the Role of K19 in Maintaining the Structural Integrity of Breast Cancer Cells

Alsharif, Sarah

Abstract

Epithelial to mesenchymal transition is associated with an initial stage of tumor metastasis when cells lose cell-cell adhesion and expression of epithelial markers such as keratin intermediate filament proteins. Keratins are critical for the shape and mechanical integrity of epithelial cells. Among different keratins, Keratin 19 (K19) is highly expressed in various types of cancer including breast cancer and is correlated with a worse patient prognosis. Consistently, K19 expression has been reported to be significantly higher in metastatic breast cancer tumor cells compared to primary tumors. Although knocking down K19 in breast cancer cells increased cell migration, recent studies have shown that increased levels of some keratins can also have a positive impact on metastasis, in part by enabling cells to invade the extracellular matrix collectively. The role of K19 on mechanical properties of cancer cells for cell migration and possible impact on metastasis in breast cancer patients is still unknown. Using K19 knockout (KO) cells in our lab, we found that K19 plays a role in maintaining epithelial cell shape and tight cell-cell adhesion of MCF7 breast cancer cells. Moreover, K19 ablation increased the migratory potential but decreased survival potential of MCF7 cells. At the molecular level, Ecadherin was surprisingly found to be overexpressed in KRT19 KO cells. However, we found that E-cadherin binding to β-catenin decreased in K19 KO cells that have less membrane-Ecadherin. Moreover, E-cadherin was found to be accumulated and internalized in early and recycling endocytic compartments in KRT19 KO cells. Inhibiting internalization of cell surface proteins restored cell-cell adhesion of KRT19 KO cells, suggesting that internalization of Ecadherin contributes to defective cell-cell 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 rounded shape and tight cellcell adhesion and this adhesion inhibits cell migration but provides growth and survival advantages for circulating tumor cells. These findings provide context-dependent roles of K19 during metastasis.

Purchased from AmBeed

Dynasore

A209594304448-55-398%

Dynasore

65.0/10mg

Detail