CHI3L1 promotes tumor progression by activating TGF-β signaling pathway in hepatocellular carcinoma.

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.

• Authors: Qing-Chong Qiu, Lin Wang, Shan-Shan Jin, Guan-Feng Liu, Jie Liu, Liang Ma, Rui-Fang Mao, Ying-Ying Ma, Na Zhao, Ming Chen, Biao-Yang Lin
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 15029 (10 09 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30301907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CHI3L1 protein, human
• Chitinase-3-Like Protein 1
• SMAD2 protein, human
• SMAD3 protein, human
• Smad2 Protein
• Smad3 Protein
• Transforming Growth Factor beta

Topics

• Animals
• Carcinogenesis (genetics)
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Proliferation (genetics)
• Chitinase-3-Like Protein 1 (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Hep G2 Cells
• Humans
• Liver Neoplasms (genetics, pathology)
• Mice
• Neoplasm Invasiveness (genetics, pathology)
• Phosphorylation
• Signal Transduction
• Smad2 Protein (genetics)
• Smad3 Protein (genetics)
• Transforming Growth Factor beta (genetics)
• Xenograft Model Antitumor Assays