Details
- Autor(en) / Beteiligte
- Titel
- β-Catenin signaling increases during melanoma progression and promotes tumor cell survival and chemoresistance
- Ist Teil von
- PloS one, 2011, Vol.6 (8), p.e23429
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek
- Beschreibungen/Notizen
- Beta-catenin plays an important role in embryogenesis and carcinogenesis by controlling either cadherin-mediated cell adhesion or transcriptional activation of target gene expression. In many types of cancers nuclear translocation of beta-catenin has been observed. Our data indicate that during melanoma progression an increased dependency on the transcriptional function of beta-catenin takes place. Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces apoptosis, inhibits proliferation, migration and invasion in monolayer and 3-dimensional skin reconstructs and decreases chemoresistance. In addition, subcutaneous melanoma growth in SCID mice was almost completely inhibited by an inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes and primary melanoma cell lines was less affected by beta-catenin depletion. However, enhanced expression of beta-catenin in primary melanoma cell lines increased invasive capacity in vitro and tumor growth in the SCID mouse model. These data suggest that beta-catenin is an essential survival factor for metastatic melanoma cells, whereas it is dispensable for the survival of benign melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin increases tumorigenicity of primary melanoma cell lines. The differential requirements for beta-catenin signaling in aggressive melanoma versus benign melanocytic cells make beta-catenin a possible new target in melanoma therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0023429Titel-ID: cdi_plos_journals_1308205341
- Format
- –
- Schlagworte
- Animals, Antigens, Antineoplastic Agents - pharmacology, Apoptosis, Benign, beta Catenin - antagonists & inhibitors, beta Catenin - genetics, beta Catenin - metabolism, Biology, Biotechnology, Cadherins, Carcinogenesis, Carcinogens, Cell activation, Cell adhesion, Cell Line, Tumor, Cell migration, Cell Movement - drug effects, Cell Proliferation - drug effects, Cell survival, Cells, Cultured, Chemoresistance, Cisplatin - pharmacology, Dermatology, Dose-Response Relationship, Drug, Doxycycline - pharmacology, Drug Synergism, Embryogenesis, Embryonic growth stage, Gene expression, Growth factors, HCT116 Cells, Humans, Kinases, Male, Medicine, Melanocytes, Melanocytes - cytology, Melanocytes - drug effects, Melanocytes - metabolism, Melanoma, Melanoma - genetics, Melanoma - metabolism, Melanoma - pathology, Melanoma, Experimental - genetics, Melanoma, Experimental - metabolism, Melanoma, Experimental - pathology, Metastases, Metastasis, Mice, Mice, SCID, Multiple myeloma, Neutropenia, Neutrophils, Nuclear transport, Perylene - analogs & derivatives, Perylene - pharmacology, RNA Interference, Signal Transduction, Signaling, Skin, Skin cancer, Survival, Survival factor, TCF Transcription Factors - antagonists & inhibitors, TCF Transcription Factors - metabolism, Toxicology, Transcription activation, Translocation, Tumor Burden - drug effects, Tumorigenicity, Xenograft Model Antitumor Assays, β-Catenin