CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell proliferation and antiapoptotic responses by binding to HSPA5 (GRP78)
Por:
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 and Sarrias, MR
Publicada:
1 jul 2018
Resumen:
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).
Filiaciones:
:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Innate Immun Grp, Badalona, Spain
Sanjurjo, L:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Innate Immun Grp, Badalona, Spain
Network Biomed Res Diabet & Associated Metab Dis, Madrid, Spain
Barcena, C:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Innate Immun Grp, Badalona, Spain
:
IGTP, Program Predict & Personalized Med Canc PMPCC, Childhood Liver Oncol Grp, Badalona, Spain
Network Biomed Res Hepat & Digest Dis CIBERehd, Madrid, Spain
:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Innate Immun Grp, Badalona, Spain
Vazquez-Vitali, M:
IGTP, Program Predict & Personalized Med Canc PMPCC, Childhood Liver Oncol Grp, Badalona, Spain
Garrido, M:
Vall Hebron Hosp, Pathol Dept, Barcelona, Spain
Guerra, L:
Hosp Univ La Paz, Pathol Dept, Madrid, Spain
Diaz, E:
Josep Trueta Hosp, Pathol Dept, Girona, Spain
Ojanguren, I:
Hosp Univ Germans Trias & Pujol Hosp HUGTiP, Pathol Dept, Badalona, Spain
Elortza, F:
Network Biomed Res Hepat & Digest Dis CIBERehd, Madrid, Spain
Ctr Cooperat Res Biosci CIC BioGUNE, Prote Platform, Derio, Spain
Planas, R:
Network Biomed Res Hepat & Digest Dis CIBERehd, Madrid, Spain
Hosp Univ Germans Trias & Pujol Hosp HUGTiP, Gastroenterol Dept, Badalona, Spain
:
Network Biomed Res Hepat & Digest Dis CIBERehd, Madrid, Spain
Hosp Univ Germans Trias & Pujol Hosp HUGTiP, Gastroenterol Dept, Badalona, Spain
:
IGTP, Program Predict & Personalized Med Canc PMPCC, Childhood Liver Oncol Grp, Badalona, Spain
Network Biomed Res Hepat & Digest Dis CIBERehd, Madrid, Spain
:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Innate Immun Grp, Badalona, Spain
Network Biomed Res Hepat & Digest Dis CIBERehd, Madrid, Spain
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