Relevancia de galectina-1 en el carcinoma hepatocelular: su contribución a la diseminación tumoral
Galectin-1 (Gal-1), a ß-galactoside-binding protein, is overexpressed in hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) represents a key step during cancer progression, enabling tissue epithelial cancers to invade and metastasize. The main objective of this Thesis consisted...
Guardado en:
| Autor principal: | |
|---|---|
| Otros Autores: | |
| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
| Publicado: |
Facultad de Farmacia y Bioquímica
2015
|
| Materias: | |
| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_829 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_829.dir/829.PDF |
| Aporte de: |
| Sumario: | Galectin-1 (Gal-1), a ß-galactoside-binding protein, is overexpressed in hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) represents a key step during cancer progression, enabling tissue epithelial cancers to invade and metastasize. The main objective of this Thesis consisted in evaluating Gal-1 contribution to HCC cell dissemination, particularly on EMT.\nIn this work, we found that Gal-1 overexpression in well differentiated HCC HepG2 cells induced the down-regulation of the epithelial markers E-cadherin and ZO-1, promoted the loss of apico-basal polarity, increased levels of the transcription factor SNAIL1 and the mesenchymal marker vimentin, enhanced HCC cell adhesion to ECM, facilitated the transition from epithelial cell morphology toward a fibroblastoid phenotype, and anchorage-independent growth. Remarkably, Gal-1 promoted AKT activation, ß-catenin phosphorylation and nuclear translocation, TCF/LEF transcriptional activity and increased cyclin D1 and cMYC expression, suggesting the hyperactivation of the WNT pathway. We also succeeded to identify a novel ligand of Gal-1 in HCC cells, prohibitin-1.\nIn conclusion, our results indicate that Gal-1 overexpression induces EMT in HepG2 HCC cells involving the PI3K/AKT/WNT/ß-catenin signaling axis. This would have critical implications in HCC metastasis, and highlight the possibility to target Gal-1 in order to restrict HCC progression. |
|---|