Reference - Detail
| RRC ID | 37056 |
|---|---|
| Author | Thang ND, Yajima I, Kumasaka MY, Iida M, Suzuki T, Kato M. |
| Title | Deltex-3-like (DTX3L) stimulates metastasis of melanoma through FAK/PI3K/AKT but not MEK/ERK pathway. |
| Journal | Oncotarget |
| Abstract |
Deltex-3-like (DTX3L), an E3 ligase, is a member of the Deltex (DTX) family and is also called B-lymphoma and BAL-associated protein (BBAP). Previously, we established RFP/RET-transgenic mice, in which systemic hyperpigmented skin, benign melanocytic tumor(s) and melanoma(s) develop stepwise. Here we showed that levels of Dtx3l/DTX3L in spontaneous melanoma in RFP/RET-transgenic mice and human melanoma cell lines were significantly higher than those in benign melanocytic cells and primarily cultured normal human epithelial melanocytes, respectively. Immunohistochemical analysis of human tissues showed that more than 80% of the melanomas highly expressed DTX3L. Activity of FAK/PI3K/AKT signaling, but not that of MEK/ERK signaling, was decreased in Dtx3l/DTX3L-depleted murine and human melanoma cells. In summary, we demonstrated not only increased DTX3L level in melanoma cells but also DTX3L-mediated regulation of invasion and metastasis in melanoma through FAK/PI3K/AKT but not MEK/ERK signaling. Our analysis in human BRAFV600E inhibitor-resistant melanoma cells showed about 80% decreased invasion in the DTX3L-depleted cells compared to that in the DTX3L-intact cells. Thus, DTX3L is clinically a potential therapeutic target as well as a potential biomarker for melanoma. |
| Volume | 6(16) |
| Pages | 14290-9 |
| Published | 2015-6-10 |
| DOI | 10.18632/oncotarget.3742 |
| PII | 3742 |
| PMID | 26033450 |
| PMC | PMC4546467 |
| MeSH | Animals Cell Line, Tumor Focal Adhesion Kinase 1 / metabolism Humans MAP Kinase Signaling System* Melanoma / enzymology Melanoma / genetics Melanoma / metabolism* Melanoma / pathology Melanoma, Experimental Mice Mice, Inbred C57BL Neoplasm Metastasis Phosphatidylinositol 3-Kinases / metabolism* Proto-Oncogene Proteins c-akt / metabolism* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* |
| IF | 5.168 |
| Times Cited | 29 |
| WOS Category | ONCOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | SK-MEL-28(RCB1930) G-361(RCB0991) |