Death inducer-obliterator 1 (Dido1) is a BMP target gene and promotes BMP-induced melanoma progression

• Published in: Oncogene Vol. 32; no. 7; pp. 837 - 848
• Main Authors: Braig, S, Bosserhoff, A-K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-02-2013; Nature Publishing Group
• Subjects: 631/67/1813/1634; 631/80/84; 631/80/84/2336; Agar; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Bone morphogenetic proteins; Bone Morphogenetic Proteins - metabolism; Bone Morphogenetic Proteins - pharmacology; Bone Morphogenetic Proteins - physiology; Care and treatment; Causes of; Cell Biology; Cell Line, Tumor; Cell lines; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Colonies; Control; Development; Development and progression; Disease Progression; DNA microarrays; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Electrophoretic mobility; Flow cytometry; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Health aspects; Human Genetics; Humans; Immunofluorescence; Integrin alphaV - genetics; Integrin alphaV - metabolism; Integrins; Internal Medicine; Medicine; Medicine & Public Health; Melanocytes; Melanoma; Melanoma - genetics; Melanoma - pathology; Metastasis; Microarray Analysis; Neoplasm Invasiveness; Oncology; original-article; Proteins; Risk factors; RNA, Small Interfering - pharmacology; siRNA; Skin cancer; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Smad protein; Smad4 Protein - antagonists & inhibitors; Smad4 Protein - genetics; Transfection; Western blotting; United States; migration; malignant melanoma; invasion; bone morphogenic protein; integrin αV
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2012.115

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.