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Title 

Plasma glutamate carboxypeptidase is a negative regulator in liver cancer metastasis

 

간암 전이 억제 조절자인 Plasma glutamate carboxypeptidase

Authors 

Jae-Hye LeeHyun Soo ChoJeong Ju LeeSoo Young JunJun Ho AhnJu-Sik MinJi-Yong YoonMin-Hyuk ChoiSu-Jin JeonJung Hwa LimCho Rok JungDae Soo KimH T KimV M FactorY H LeeS S ThorgeirssonC H KimNam-Soon Kim

Publisher 

Impact Journals

Issue Date 

2016

Citation 

Oncotarget

Keywords 

Liver cancerMetastasisPGCPWnt/β-catenin

Abstract 

Tumor metastasis is the leading cause of cancer death. In the metastatic process, EMT is a unique phenotypic change that plays an important role in cell invasion and changes in cell morphology. Despite the clinical significance, the mechanism underlying tumor metastasis is still poorly understood. Here we report a novel mechanism by which secreted plasma glutamate carboxypeptidase(PGCP) negatively involves Wnt/β-catenin signaling by DKK4 regulation in liver cancer metastasis. Pathway analysis of the RNA sequencing data showed that PGCP knockdown in liver cancer cell lines enriched the functions of cell migration, motility and mesenchymal cell differentiation. Depletion of PGCP promoted cell migration and invasion via activation of Wnt/β-catenin signaling pathway components such as phospho-LRP6 and β-catenin. Also, addition of DKK4 antagonized the Wnt/β-catenin signaling cascade in a thyroxine (T4)-dependent manner. In an in vivo study, metastatic nodules were observed in the lungs of the mice after injection of shPGCP stable cell lines. Our findings suggest that PGCP negatively associates with Wnt/β-catenin signaling during metastasis. Targeting this regulation may represent a novel and effective therapeutic option for liver cancer by preventing metastatic activity of primary tumor cells.

ISSN 

1949-2553

Link 

http://dx.doi.org/10.18632/oncotarget.12967

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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