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CHI3L1 promotes tumor progression by activating TGF-β signaling pathway in hepatocellular carcinoma
- Source :
- Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
- Publication Year :
- 2018
-
Abstract
- CHI3L1 (YKL40) is a secreted glycoprotein and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in many human cancers. However, the mechanism of how CHI3L1 causes poor prognosis in cancers is still unknown. Here, considering that CHI3L1 is a liver specific/enriched protein, we use hepatocellular carcinoma as a model to study the function of CHI3L1. We showed that, both in vivo and in vitro, overexpression of CHI3L1 could promote liver cancer cells growth, migration and invasion. We then used RNA-seq to analyze the expression profiles of CHI3L1 overexpressed in two HCC cell lines and found that CHI3L1 overexpression affected genes that were involved in cell-cell adhesion, extracellular exosome and adherens junction. Western blot analysis further revealed that CHI3L1 could activate TGF-β signal pathways. Our data added new understanding of the mechanism of CHI3L1’s action. 1) CHI3L1 promoted cancer cell proliferation by regulating cell cycles; 2) CHI3L1 promoted cancer cell invasion and metastasis; 3) CHI3L1 regulate liver cancer potentially by regulating the TGF-β signaling pathways; 4) CHI3L1 has direct kinase activities or activate kinase to phosphorylate SMAD2, SMAD3.
- Subjects :
- 0301 basic medicine
Carcinoma, Hepatocellular
Epithelial-Mesenchymal Transition
Carcinogenesis
lcsh:Medicine
Smad2 Protein
Biology
Article
Metastasis
Adherens junction
03 medical and health sciences
Mice
0302 clinical medicine
Transforming Growth Factor beta
Extracellular exosome
medicine
Animals
Humans
Neoplasm Invasiveness
Chitinase-3-Like Protein 1
Smad3 Protein
Phosphorylation
lcsh:Science
Cell Proliferation
Multidisciplinary
lcsh:R
Liver Neoplasms
Hep G2 Cells
Cell cycle
medicine.disease
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
030104 developmental biology
Tumor progression
030220 oncology & carcinogenesis
Cancer cell
Cancer research
lcsh:Q
Signal transduction
Liver cancer
Signal Transduction
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....2cc3c028c27a544d0dd7442a4687b24c