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Open AccessArticle

A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan
Department of Anatomy, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2016, 17(11), 1846;
Received: 31 August 2016 / Revised: 1 November 2016 / Accepted: 2 November 2016 / Published: 5 November 2016
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. View Full-Text
Keywords: Dickkopf-3; macropinocytosis; autophagy; nutrition Dickkopf-3; macropinocytosis; autophagy; nutrition
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Tsujimura, N.; Yamada, N.O.; Kuranaga, Y.; Kumazaki, M.; Shinohara, H.; Taniguchi, K.; Akao, Y. A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells. Int. J. Mol. Sci. 2016, 17, 1846.

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