A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells.
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.
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. nono.pi306@gmail.com.
Nonoka
N
Tsujimura
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. nyamada@gifu-u.ac.jp.|Department of Anatomy, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. nyamada@gifu-u.ac.jp.
Nami O
NO
Yamada
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. v3501001@edu.gifu-u.ac.jp.
Yuki
Y
Kuranaga
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. t3501001@edu.gifu-u.ac.jp.
Minami
M
Kumazaki
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. harukashinohara313@gmail.com.
Haruka
H
Shinohara
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. sur144@osaka-med.ac.jp.
Kohei
K
Taniguchi
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1194, Japan. yakao@gifu-u.ac.jp.
Yukihiro
Y
Akao
D048868:Adaptor Proteins, Signal Transducing; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010873:Pinocytosis / Q000187:drug effects / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
D048868:Adaptor Proteins, Signal Transducing; D000225:Adenine; D000584:Amiloride; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D051907:Lysosomal Membrane Proteins; D048670:MAP Kinase Kinase 4; D035683:MicroRNAs; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; D020696:rab5 GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; C498624:DKK3 protein, human; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C541874:MIRN92 microRNA, human; C107953:RAC1 protein, human; C025946:3-methyladenine; C535150:MAPK1 protein, human; C427755:RAB5C protein, human; C039614:ethylisopropylamiloride
Dickkopf-3; autophagy; macropinocytosis; nutrition