Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells.
Deregulation of Wnt/beta-catenin signaling is thought to play a critical role in human carcinogenesis. Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase that suppresses beta-catenin/T-cell factor (TCF) complex transcriptional activity through phosphorylation of TCF. Since NLK may be a tumor suppressor as a negative regulator of Wnt/beta-catenin pathway, we established tetracycline-inducible NLK and its kinase-negative mutant expression in DLD-1 human colon cancer cells to analyze the effect of NLK on cell growth and viability. The induction of wild-type NLK in DLD-1 cells caused suppression of cell growth whereas the kinase-negative mutant did not. Flow cytometry indicated that NLK expression increased the number of apoptotic cells but did not induce obvious cell cycle arrest. Apoptosis induction by wild-type NLK was confirmed using TUNEL assays. Our results suggest that overexpression of NLK may have targets other than TCF for induction of apoptosis in human colon carcinoma cells.
Yasuda
Jun
J
Cancer Transcriptome Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. jyasuda@ncc.go.jp
Tsuchiya
Akira
A
Yamada
Tesshi
T
Sakamoto
Michiie
M
Sekiya
Takao
T
Hirohashi
Setsuo
S
D017209:Apoptosis / Q000502:physiology*; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D004790:Enzyme Induction; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051176:beta Catenin; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases