Title |
Sema6A and Mical1 control cell growth and survival of BRAF V600E human melanoma cells
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Published in |
Oncotarget, December 2014
|
DOI | 10.18632/oncotarget.2995 |
Pubmed ID | |
Authors |
Rossella Loria, Giulia Bon, Valentina Perotti, Enzo Gallo, Ilaria Bersani, Paola Baldassari, Manuela Porru, Carlo Leonetti, Selene Di Carlo, Paolo Visca, Maria Felice Brizzi, Andrea Anichini, Roberta Mortarini, Rita Falcioni |
Abstract |
We used whole genome microarray analysis to identify potential candidate genes with differential expression in BRAFV600E vs NRASQ61R melanoma cells. We selected, for comparison, a peculiar model based on melanoma clones, isolated from a single tumor characterized by mutually exclusive expression of BRAFV600E and NRASQ61R in different cells. This effort led us to identify two genes, SEMA6A and MICAL1, highly expressed in BRAF-mutant vs NRAS-mutant clones. Real-time PCR, Western blot and immunohistochemistry confirmed preferential expression of Sema6A and Mical1 in BRAFV600E melanoma. Sema6A is a member of the semaphorin family, and it complexes with the plexins to regulate actin cytoskeleton, motility and cell proliferation. Silencing of Sema6A in BRAF-mutant cells caused cytoskeletal remodeling, and loss of stress fibers, that in turn induced cell death. Furthermore, Sema6A depletion caused loss of anchorage-independent growth, inhibition of chemotaxis and invasion. Forced Sema6A overexpression, in NRASQ61R clones, induced anchorage-independent growth, and a significant increase of invasiveness. Mical1, that links Sema/PlexinA signaling, is also a negative regulator of apoptosis. Indeed, Mical-1 depletion in BRAF mutant cells restored MST-1-dependent NDR phosphorylation and promoted a rapid and massive NDR-dependent apoptosis. Overall, our data suggest that Sema6A and Mical1 may represent new potential therapeutic targets in BRAFV600E melanoma. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 50 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 11 | 22% |
Student > Ph. D. Student | 9 | 18% |
Student > Master | 7 | 14% |
Student > Doctoral Student | 3 | 6% |
Student > Bachelor | 3 | 6% |
Other | 8 | 16% |
Unknown | 9 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 19 | 38% |
Agricultural and Biological Sciences | 11 | 22% |
Medicine and Dentistry | 6 | 12% |
Neuroscience | 2 | 4% |
Social Sciences | 1 | 2% |
Other | 1 | 2% |
Unknown | 10 | 20% |