Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells

Rossella Loria, Giulia Bon, Valentina Perotti, Enzo Gallo, Ilaria Bersani, Paola Baldassari, Manuela Porru, Carlo Leonetti, Selene Di Carlo, Paolo Visca, Maria F elice Brizzi, Andrea Anichini, Roberta Mortarini, Rita Falcioni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2779-2793
Number of pages15
JournalOncotarget
Volume6
Issue number5
Publication statusPublished - Feb 20 2015

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Melanoma
Cell Survival
Clone Cells
Growth
Cell Migration Inhibition
Semaphorins
Apoptosis
Stress Fibers
Microarray Analysis
Actin Cytoskeleton
Genes
Real-Time Polymerase Chain Reaction
Cell Death
Western Blotting
Immunohistochemistry
Phosphorylation
Cell Proliferation
Genome
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Loria, R., Bon, G., Perotti, V., Gallo, E., Bersani, I., Baldassari, P., ... Falcioni, R. (2015). Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells. Oncotarget, 6(5), 2779-2793.

Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells. / Loria, Rossella; Bon, Giulia; Perotti, Valentina; Gallo, Enzo; Bersani, Ilaria; Baldassari, Paola; Porru, Manuela; Leonetti, Carlo; Di Carlo, Selene; Visca, Paolo; Brizzi, Maria F elice; Anichini, Andrea; Mortarini, Roberta; Falcioni, Rita.

In: Oncotarget, Vol. 6, No. 5, 20.02.2015, p. 2779-2793.

Research output: Contribution to journalArticle

Loria, R, Bon, G, Perotti, V, Gallo, E, Bersani, I, Baldassari, P, Porru, M, Leonetti, C, Di Carlo, S, Visca, P, Brizzi, MFE, Anichini, A, Mortarini, R & Falcioni, R 2015, 'Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells', Oncotarget, vol. 6, no. 5, pp. 2779-2793.
Loria R, Bon G, Perotti V, Gallo E, Bersani I, Baldassari P et al. Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells. Oncotarget. 2015 Feb 20;6(5):2779-2793.
Loria, Rossella ; Bon, Giulia ; Perotti, Valentina ; Gallo, Enzo ; Bersani, Ilaria ; Baldassari, Paola ; Porru, Manuela ; Leonetti, Carlo ; Di Carlo, Selene ; Visca, Paolo ; Brizzi, Maria F elice ; Anichini, Andrea ; Mortarini, Roberta ; Falcioni, Rita. / Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells. In: Oncotarget. 2015 ; Vol. 6, No. 5. pp. 2779-2793.
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