Lysosomal Degradation of CD44 Mediates Ceramide Nanoliposome-induced Anoikis and Diminshed Extravasation in Metastatic Carcinoma Cells [Molecular Bases of Disease]
February 13th, 2015 by Haakenson, J. K., Khokhlatchev, A. V., Choi, Y. J., Linton, S. S., Zhang, P., Zaki, P. M., Fu, C., Cooper, T. K., Manni, A., Zhu, J., Fox, T. E., Dong, C., Kester, M.
The ceramide nanoliposome (CNL) has shown promise in being able to treat a variety of primary tumors. However, its potential for treating metastatic cancer remains unknown. In this study, we demonstrate that CNL increases anoikis, while preventing cancer cell extravasation under both static and physiological fluid flow conditions. Mechanistically, CNL limits metastases by decreasing CD44 protein levels in human breast and pancreatic cancer cells via lysosomal degradation of CD44, independent of palmitoylation or proteasome targeting. SiRNA down regulation of CD44 mimics CNL-induced anoikis and diminished extravasation of cancer cells. Taken together, our data indicate that ceramide limits CD44-dependent cancer cell migration, suggesting that CNL could be used to prevent and treat solid tumor metastasis.