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ISG15 promotes esophageal squamous cell carcinoma tumorigenesis via c-MET/Fyn/β-catenin signaling pathway.
- Source :
-
Experimental cell research [Exp Cell Res] 2018 Jun 01; Vol. 367 (1), pp. 47-55. Date of Electronic Publication: 2018 Mar 17. - Publication Year :
- 2018
-
Abstract
- Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in China with a poor prognosis. Most ESCC patients were diagnosed at advanced stages, losing the opportunity for surgical excision. Hence, it remains a pressing work to identify biomarkers for early detection, prognosis prediction and targeting therapies in ESCC. Interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, and is involved in the post-translational modification (PTMs) of multiple proteins. However, the molecular functions of ISG15 in ESCC remain unclear. In this work, we found that ISG15 was aberrantly expressed in ESCC tissues and cell lines. Enhanced protein level of ISG15 promoted cellular malignant phenotypes including proliferation, migration, invasion and tumor formation in vivo. Consistently, reduction of ISG15 attenuated the cellular malignant phenotype in ESCC cell lines. Furthermore, gene-expression profiles suggested that the differentially expressed ISG15 affected the expression of a panel of genes enriched in the cell adherens junction, such as c-MET. Notably, as a secreted protein, the concentration of ISG15 was elevated in ESCC plasma than healthy individuals, acting as a potential diagnostic marker. Taken together, our results suggested a tumor promotion role of ISG15 in ESCC via c-MET/Fyn/β-catenin pathway.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Cell Line, Tumor
Cytokines genetics
Esophageal Neoplasms pathology
Esophageal Squamous Cell Carcinoma pathology
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Proto-Oncogene Proteins c-fyn genetics
Receptor Protein-Tyrosine Kinases genetics
Ubiquitins genetics
Xenograft Model Antitumor Assays
beta Catenin genetics
beta Catenin metabolism
Carcinogenesis genetics
Cytokines physiology
Esophageal Neoplasms genetics
Esophageal Squamous Cell Carcinoma genetics
Proto-Oncogene Proteins c-fyn metabolism
Receptor Protein-Tyrosine Kinases metabolism
Ubiquitins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 367
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 29555370
- Full Text :
- https://doi.org/10.1016/j.yexcr.2018.03.017