Open AccessAntitumor efficacy of C ‐ X ‐ C motif chemokine ligand 14 in hepatocellular carcinoma in vitro and in vivo
Author(s) -
Wang Weilin,
Huang Pengfei,
Zhang Lufei,
Wei Jianfeng,
Xie Qingsong,
Sun Qiang,
Zhou Xiaohu,
Xie Haiyang,
Zhou Lin,
Zheng Shusen
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12279
Subject(s) - cxcl14 , cancer research , downregulation and upregulation , apoptosis , cell growth , chemokine , biology , cell cycle , pancreatic cancer , chemokine receptor , microbiology and biotechnology , immunology , cancer , immune system , biochemistry , genetics , gene
C ‐ X ‐ C motif chemokine ligand 14 ( CXCL 14) is a novel gene that is expressed in many normal cells but is absent from or expressed at very low levels in cancerous tissues such as head and neck squamous cell carcinoma ( HNSCC ), prostate cancer, and pancreatic cancer. However, the relationship between CXCL 14 and hepatocellular carcinoma ( HCC ) remains unclear. Therefore, the exact function of CXCL 14, which may modulate antitumor immune responses in certain cancers, was evaluated. CXCL 14 was downregulated in HCC tissues compared to adjacent normal tissues. Moreover, overexpression of CXCL 14 had an inhibitory effect on cell proliferation, induced apoptosis and inhibited the invasion of HCC cells in vitro . Upregulation of CXCL 14 by lentivirus also significantly suppressed the growth of subcutaneous tumors in nude mice in vivo . We further demonstrated that the loss of CXCL 14 expression was regulated by promoter hypermethylation. CXCL 14 induced tumor cell apoptosis through both the mitochondrial and nuclear apoptosis pathways. CXCL 14 suppressed tumor cell proliferation through regulation of the cell cycle by downregulation of cyclins and cyclin‐dependent kinases. In conclusion, CXCL 14 plays a pivotal role as a potential tumor suppressor in HCC . The re‐expression or upregulation of this gene may provide a novel strategy in HCC therapy in the future.