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Death inducer-obliterator 1 (Dido1) is a BMP target gene and promotes BMP-induced melanoma progression.
- Source :
-
Oncogene [Oncogene] 2013 Feb 14; Vol. 32 (7), pp. 837-48. Date of Electronic Publication: 2012 Apr 02. - Publication Year :
- 2013
-
Abstract
- Bone morphogenetic proteins (BMPs) are known to play an important role in melanoma development and progression. However, the downstream targets of BMPs have not been investigated thus far. Therefore, we treated melanoma cell lines with the Smad-specific BMP inhibitor Dorsomorphin and performed a cDNA microarray. We identified death inducer-obliterator 1 (Dido1) as a BMP-specific Smad-regulated target gene, which was confirmed by qRT-PCR, immunofluorescence staining and electrophoretic mobility shift assay experiments. An analysis of Dido1 expression revealed an upregulation of Dido1 levels in melanoma cell lines and tissues compared with normal melanocytes. Colony-formation assays showed that siDido1-transfected cells formed significantly smaller colonies when grown in soft agar compared with control cells. In addition, fluorescence-activated cell sorting and western blot experiments revealed that transfection of melanoma cells with Dido1 small interfering RNAs led to an upregulation of apoptosis. Furthermore, cell migratory and invasive potentials were strongly reduced in siDido1-transfected cells compared with control cells. Finally, we demonstrated that Dido1 induces the expression of Integrin αV, thereby promoting the attachment, migration, invasion and apoptosis resistance of melanoma cells.
- Subjects :
- Apoptosis drug effects
Apoptosis genetics
Bone Morphogenetic Proteins metabolism
Bone Morphogenetic Proteins physiology
Cell Line, Tumor
Cell Movement drug effects
Cell Movement genetics
DNA-Binding Proteins antagonists & inhibitors
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Disease Progression
Gene Expression Profiling
Humans
Integrin alphaV genetics
Integrin alphaV metabolism
Melanoma pathology
Microarray Analysis
Neoplasm Invasiveness
RNA, Small Interfering pharmacology
Skin Neoplasms pathology
Smad4 Protein antagonists & inhibitors
Smad4 Protein genetics
Bone Morphogenetic Proteins pharmacology
DNA-Binding Proteins physiology
Gene Expression Regulation, Neoplastic drug effects
Melanoma genetics
Skin Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 32
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 22469980
- Full Text :
- https://doi.org/10.1038/onc.2012.115