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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/223486
Regulatory Mechanisms of SPARC Overexpression in Melanoma Progression
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The expression of the Secreted Protein, Acidic and Rich in Cysteine (SPARC) gene in human melanoma increases during progression and is associated with epithelial-to-mesenchymal transition (EMT), which is a major determinant of metastasis in melanoma patients. However, the underlying molecular mechanisms that control SPARC expression in this context remain elusive. Herein, we identified Paired-related homeobox 1 (PRRX1), an EMT transcription factor, as a transcriptional activator of SPARC by direct binding to the promoter, thereby increasing its activity. Moreover, we found a strong positive correlation between SPARC and PRRX1 expression levels in clinical samples and cell lines. Furthermore, the switch from the proliferative/melanocytic phenotype toward the invasive/mesenchymal-like phenotype favors the expression of TCF7L2, a beta-catenin cofactor, which, together with Sp1, binds to the proximal SPARC promoter, thereby bolstering protein expression. We also show that SPARC is a target of the miR-29 family, whose members are expressed in clinical melanoma samples and cell lines. Indeed, we found that miR-29b1 similar to a expression is inversely correlated with SPARC levels, and it is significantly reduced in samples with a mesenchymal-like phenotype. Taken together, SPARC expression in melanoma cells relies on transcriptional activation by PRRX1/TCF7L2-Sp1 and is modulated through miR-29b1 similar to a, which provides fine-tuning regulation over the switch between phenotypic states.
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VINYALS, Antònia, FERRERES RIERA, Jose ramon, CAMPOS MARTÍN, Rafael, JORGE TORRES, Olga c., MAINEZ VILLORO, Jessica, PUIG BUTILLÉ, Joan anton, MARCOVAL CAUS, Joaquim, PUIG I SARDÀ, Susana, FABREGAT ROMERO, Isabel, FABRA FRES, Àngels. Regulatory Mechanisms of SPARC Overexpression in Melanoma Progression. _International Journal of Molecular Sciences_. 2025. Vol. 26, núm. 17, pàgs. 8743. [consulta: 3 de gener de 2026]. ISSN: 1422-0067. [Disponible a: https://hdl.handle.net/2445/223486]