INVESTIGADORES
PODHAJCER Osvaldo Luis
artículos
Título:
SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen I/α2β1 integrin axis
Autor/es:
MARÍA ROMINA GIROTTI; MARISOL FERNÁNDEZ RODRÍGUEZ; JUAN ANTONIO LÓPEZ; EMILIO CAMAFEITA; ELMER FERNÁNDEZ; JUAN PABLO ALBAR; LORENA GABRIELA BENEDETTI; MARÍA PÍA VALACCO; ROLF BREKKEN; OSVALDO LUIS PODHAJCER; ANDREA SABINA LLERA
Revista:
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2011 p. 2438 - 2447
ISSN:
0022-202X
Resumen:
In melanoma, the extracellular protein SPARC (secreted protein acidic
and rich in cysteine) is related to tumor progression. Some of the
evidence that links SPARC to melanoma progression indicates that SPARC
may be involved in the acquisition of mesenchymal traits that favor
metastatic dissemination. However, no molecular pathways that link
extracellular SPARC to a mesenchymal phenotype have been described. In
this study, global protein expression analysis of the melanoma secretome
following enforced downregulation of SPARC expression led us to
elucidate a new molecular mechanism by which SPARC promotes cathepsin
B-mediated melanoma invasiveness using collagen I and α2β1 integrins as
mediators. Interestingly, we also found that the transforming growth
factor (TGF)-β1 contribution to cathepsin B-mediated invasion is highly
SPARC dependent. In addition, induction of the E-cadherin to N-cadherin
switch by SPARC enabled melanoma cells to transmigrate across an
endothelial layer through a mechanism independent to that of enhancing
invasion. Finally, SPARC also enhanced the extracellular expression of
other proteins involved in epithelial-mesenchymal transformation, such
as family with sequence similarity 3, member C/interleukin-like
EMT-inducer. Our findings demonstrate a previously unreported molecular
pathway for SPARC activity on invasion and support an active role of
SPARC in the mesenchymal transformation that contributes to melanoma
dissemination.