E‐cadherin‐Fc chimera protein matrix enhances cancer stem‐like properties and induces mesenchymal features in colon cancer cells

摘要

Cancer stem cells ( ) are a subpopulation of tumor cells with properties of high tumorigenicity and drug resistance, which lead to recurrence and poor prognosis. Although a better understanding of is essential for developing cancer therapies, scarcity of the population has hindered such analyses. The aim of the present study was to elucidate whether the E‐cadherin‐Fc chimera protein (E‐cad‐Fc) enhances cancer stem‐like properties because studies show that soluble E‐cadherin stimulates human epithelial growth factor receptor ( ) and downstream signaling pathways that are reported to play a crucial role in . For this purpose, we used ornithine decarboxylase ( )‐degron–transduced (Degron(+)) 12 cells as a model that retains relatively low properties. Compared to cultures without E‐cad‐Fc treatment, we found that E‐cad‐Fc treatment further suppressed proteasome activity and largely enhanced cancer stem‐like properties of ‐degron–transduced 12 cells. These results include increased expression of stem cell markers Lgr5, Bmi‐1, 9, 44, and 44v9, aldehyde dehydrogenase ( ), and enhancement of robust spheroid formation, and chemoresistance to 5‐fluorouracil (5‐ ) and oxaliplatin (L‐ ). These effects could be attributed to activation of the pathway as identified by extensive phosphorylation of , , 3K, , and . In 480 cells, E‐cad‐Fc matrix induced some markers such as 44v9 and . We also found that E‐cad‐Fc matrix showed high efficiency of inducing mesenchymal changes in colon cancer cells. Our data suggest that the E‐cad‐Fc matrix may enhance properties such as enhancement of chemoresistance and sphere formation.