RRC ID 56924
著者 Hou J, Ge C, Cui M, Liu T, Liu X, Tian H, Zhao F, Chen T, Cui Y, Yao M, Li J, Li H.
タイトル Pigment epithelium-derived factor promotes tumor metastasis through an interaction with laminin receptor in hepatocellular carcinomas.
ジャーナル Cell Death Dis
Abstract Pigment epithelium-derived factor (PEDF) has complex functions in tumor metastasis, but little is known about the roles of PEDF and its receptors in hepatocellular carcinoma (HCC). Here we found that high expression of PEDF is associated with shorter overall survival in HCC patients. Forced expression of PEDF enhanced HCC cell aggressive behavior in vitro and in vivo, whereas silencing PEDF expression reduced migration and invasion. Furthermore, PEDF expression led to changes in cell morphology and the expression of epithelial-mesenchymal transition (EMT)-related markers via ERK1/2 signaling pathway, including the upregulation of N-cadherin and slug, and the downregulation of E-cadherin in HCC cells. Our results further showed that PEDF could interact with laminin receptor (LR) and LR knockdown attenuated PEDF-induced migration, invasion and the change of EMT-related markers. More importantly, in clinical HCC specimens, we found that PEDF expression was correlated with subcellular localization of LR, and that high expression of PEDF and positive expression of LR predicted a poor prognosis. In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.
巻・号 8(8)
ページ e2969
公開日 2017-8-3
DOI 10.1038/cddis.2017.359
PII cddis2017359
PMID 28771223
PMC PMC5596550
MeSH Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Movement Eye Proteins / genetics Eye Proteins / metabolism* Humans Liver Neoplasms / genetics Liver Neoplasms / metabolism* Liver Neoplasms / pathology MAP Kinase Signaling System* Mitogen-Activated Protein Kinase 1 / genetics Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / genetics Mitogen-Activated Protein Kinase 3 / metabolism Neoplasm Metastasis Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Nerve Growth Factors / genetics Nerve Growth Factors / metabolism* Receptors, Laminin / genetics Receptors, Laminin / metabolism* Serpins / genetics Serpins / metabolism*
IF 5.959
引用数 9
リソース情報
ヒト・動物細胞 HuH-7