ï¿½ 2016 by the authors; licensee MDPI, Basel, Switzerland. Dickkopf-related protein 3 (Dkk-3) is a potential tumor suppressor reported in various cancer entities. However, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells. To validate the biological role of Dkk-3 other than a tumor suppressor, we examined the function of Dkk-3 in T24 cells. Gene silencing of Dkk-3 inhibited cell growth through inducing G0/G1 cell-cycle arrest. Furthermore, Dkk-3 knock-down caused macropinocytosis accompanied by autophagy, which were canceled in part by their inhibitors 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methyladenine (3-MA). The macropinocytosis was induced by the Dkk-3 knock-down when there were sufficient extracellular nutrients. On the other hand, when the nutritional condition was poor, the autophagy was mainly induced by the Dkk-3 knock-down. These data indicated that Dkk-3 has a role in modulating macropinocytotic and autophagic pathways, a distinct function other than a Wnt antagonist.
Tsujimura, N., Yamada, N. O., Kuranaga, Y., Kumazaki, M., Shinohara, H., Taniguchi, K., & Akao, Y. (2016). A novel role of dickkopf-related protein 3 in macropinocytosis in human bladder cancer T24 cells. International Journal of Molecular Sciences, 17(11). https://doi.org/10.3390/ijms17111846