IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
Galectin-1 triggers epithelial-mesenchymal transition in human hepatocellular carcinoma cells",
Autor/es:
BACIGALUPO, MARÍA LORENA; MANZI, MALENA; ESPELT, MARÍA V.; GENTILINI, LUCAS; COMPAGNO, DANIEL O.; LADERACH, DIEGO; WOLFENSTEIN, CARLOTA; RABINOVICH, GABRIEL A.; TRONCOSO, MARÍA FERNANDA
Revista:
JOURNAL OF CELLULAR PHYSIOLOGY
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2015 vol. 230 p. 1298 - 1309
ISSN:
0021-9541
Resumen:
Galectin-1 (Gal1), a b-galactoside-binding protein abundantly expressed in tumor microenvironments, is associated with the developmentof metastasis in hepatocellular carcinomas (HCC). However, the precise roles of Gal1 in HCC cell invasiveness and dissemination areuncertain. Here, we investigated whether Gal1 mediate epithelial-mesenchymal transition (EMT) in HCC cells, a key process during cancerprogression. We used the well-differentiated and low invasive HepG2 cells and performed ?gain-of-function? and ?loss-function?experiments by transfecting cells with Gal1 cDNA constructs or by siRNA strategies, respectively. Epithelial and mesenchymal markersexpression, changes in apico-basal polarity, independent-anchorage growth, and activation of specific signaling pathways were studied usingWestern blot, fluorescence microscopy, soft-agar assays, and FOP/TOP flash reporter system. Gal1 up-regulation in HepG2 cells induceddown-regulation of the adherens junction protein E-cadherin and increased expression of the transcription factor Snail, one of the maininducers of EMT in HCC. Enhanced Gal1 expression facilitated the transition from epithelial cell morphology towards a fibroblastoidphenotype and favored up-regulation of the mesenchymal marker vimentin in HCC cells. Cells overexpressing Gal1 showed enhancedanchorage-independent growth and loss of apico-basal polarity. Remarkably, Gal1 promoted Akt activation, b-catenin nucleartranslocation, TCF4/LEF1 transcriptional activity and increased cyclin D1 and c-Myc expression, suggesting activation of the Wnt pathway.Furthermore, Gal1 overexpression induced E-cadherin downregulation through a PI3K/Akt-dependent mechanism. Our results providethe first evidence of a role of Gal1 as an inducer of EMT in HCC cells, with critical implications in HCC metastasis.