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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Metastasis | Primary research

The Hippo signaling effector WWTR1 is a metastatic biomarker of gastric cardia adenocarcinoma

Authors: Jing Wei, Lincui Wang, Jun Zhu, Aiqin Sun, Guanzhen Yu, Miao Chen, Pan Huang, Hanqing Liu, Genbao Shao, Wannian Yang, Qiong Lin

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

Gastric cardia adenocarcinoma (GCA) is an aggressive subtype of gastric cancer with a high metastatic rate. However, the metastatic biomarker of GCA has not been established.

Methods

To search for the biomarker for GCA metastasis, we here examined expression of the Hippo signaling effector WWTR1 (WW domain containing transcription regulator 1, commonly listed as TAZ) in tumor tissue samples from 214 GCA cases using the tissue microarray assay (TMA), and statistically analyzed association of the WWTR1 expression with metastasis-related pathological outcomes and cumulative survival of the GCA patients. Furthermore, shRNA knockdown was used to determine the role of WWTR1 in promoting cell migration in gastric cancer cells.

Results

The results have shown that WWTR1 is overexpressed in 66.4% of the GCA tumor samples. Expression of WWTR1 has a significant inverse correlation with cumulative survival of GCA patients (p < 0.01). WWTR1 positive patients had a mean survival of 56.9 ± 4.4 months, comparing to WWTR1 negative mean survival of 77.3 ± 5.9 months. More importantly, expression of WWTR1 significantly associated with tumor invasion and metastasis (in T stage, p = 0.031; N stage, p < 0.01; and TNM stage, p < 0.001). Furthermore, knockdown of WWTR1 impaired migration of gastric cancer AGS cells.

Conclusions

Our studies have identified WWTR1 as a metastatic biomarker of GCA for poor prognosis, defined a role of WWTR1 in driving metastasis of gastric cancer, and suggested WWTR1 as a potential target for anti-metastatic therapy of GCA.
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Metadata
Title
The Hippo signaling effector WWTR1 is a metastatic biomarker of gastric cardia adenocarcinoma
Authors
Jing Wei
Lincui Wang
Jun Zhu
Aiqin Sun
Guanzhen Yu
Miao Chen
Pan Huang
Hanqing Liu
Genbao Shao
Wannian Yang
Qiong Lin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0796-z

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