CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell proliferation and antiapoptotic responses by binding to HSPA5 (GRP78)
| Autor: | Ramon Planas, Maria-Rosa Sarrias, Marina Simon-Coma, Margarita Sala, Érica Téllez, Marta Garrido, Carolina Armengol, Esther Díaz, Cristina Bárcena, Maria Vázquez-Vitali, Lucía Sanjurjo, Gemma Aran, Laura Guerra, Felix Elortza, Isabel Ojanguren |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Hepatoblastoma Small interfering RNA Carcinoma Hepatocellular immunoglobulin protein Apoptosis Biochemistry 03 medical and health sciences Heat shock protein Genetics medicine Humans Endoplasmic Reticulum Chaperone BiP Molecular Biology Heat-Shock Proteins Aged Cell Proliferation Aged 80 and over Receptors Scavenger soluble protein Cell growth Chemistry cirrhosis Liver Neoplasms Hep G2 Cells Middle Aged Scavenger Receptors Class B hepatoblastoma medicine.disease Up-Regulation 030104 developmental biology Cell culture Hepatocellular carcinoma Unfolded Protein Response Cancer research Female Apoptosis Regulatory Proteins Liver cancer Protein Binding Biotechnology |
| Zdroj: | FASEB Journal r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname |
| ISSN: | 1530-6860 |
| Popis: | CD5-like (CD5L) is a soluble scavenger cysteine-rich protein that modulates inflammatory responses. We studied the involvement of CD5L in liver cancer. Immunohistochemistry (IHC) of CD5L in 60 hepatocellular carcinomas and 34 adjacent nontumor livers, showed that CD5L staining was higher in tumor than in nontumor tissue (Mann-Whitney test; P = 0.0039). High CD5L correlated with elevated proliferation (Ki67, linear regression; P < 0.0001) and lower patient event-free survival (log-rank; P = 0.0185). Accordingly, CD5L expression was detected in the liver cancer cell lines Huh7, HepG2, and SNU-398. In vitro technologies using these cell lines, including small interfering RNA (siRNA) and cDNA transfection, showed that CD5L promoted colony formation and cell proliferation and protected against cisplatin-induced apoptosis. To find a molecular explanation for these roles, novel CD5L-interacting protein ligands in liver cancer cells were identified by immunoprecipitation followed by mass spectrometry. Among these, the molecular chaperone of the unfolded protein response (UPR), heat shock protein (HSP)-A5, was selected for validation. The interaction was confirmed by confocal microscopy in the Huh7 and HepG2 cell lines. Furthermore, functional experiments revealed that CD5L activates the UPR and autophagy mechanisms in Huh7 cells, thereby providing a novel molecular link between the UPR and autophagy in liver cancer.-Aran, G., Sanjurjo, L., Barcena, C., Simon-Coma, M., Tellez, E., Vazquez-Vitali, M., Garrido, M., Guerra, L., Diaz, E., Ojanguren, I., Elortza, F., Planas, R., Sala, M., Armengol, C., Sarrias, M.-R. CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell proliferation and antiapoptotic responses by binding to HSPA5 (GRP78). |
| Databáze: | OpenAIRE |
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