Constitutive activation of Wnt/beta-catenin signaling pathway in migration-active melanoma cells: role of LEF-1 in melanoma with increased metastatic potential.
A constitutive complex of beta-catenin and LEF-1 has been detected in melanoma cell lines expressing either mutant beta-catenin or mutant APC (Rubinfeld et al., Science, 275, 1790-1792, 1997). However, it has been recently reported that beta-catenin mutations are rare in primary malignant melanoma, but its nuclear and/or cytoplasmic localization, a potential indicator of Wnt/beta-catenin pathway activation, is frequently observed in melanoma (Rimm et al., Am. J. Pathol., 154, 325-329, 1999). In human malignant melanoma, the appearance of the tumorigenic phase represents a capacity for metastasis and is the significant phenotypic step in disease progression. Cell motility in invasive melanoma is thought to play a crucial role in metastatic behavior. In this work, we sought to determine which transcription factor of the LEF/TCF family was preferentially involved in human melanoma from different stages of tumor progression. We show that LEF-1 mRNA expression is predominant in highly migrating cells from metastatic melanomas. These actively migrating melanoma cells showed nuclear and cytoplasmic accumulation of beta-catenin and active transcription from a reporter plasmid of the LEF/TCF binding site. These results may provide a new insight into the role of the Wnt/beta-catenin signaling pathway in the tumor progression of malignant melanoma.
Murakami
T
T
Department of Dermatology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan. takmu@jichi.ac.jp
Toda
S
S
Fujimoto
M
M
Ohtsuki
M
M
Byers
H R
HR
Etoh
T
T
Nakagawa
H
H
D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin