Open Access Highly Accessed Research article

Glucose-regulated protein 58 modulates β-catenin protein stability in a cervical adenocarcinoma cell line

Chia-Jung Liao1, Tzu-I Wu12, Ya-Hui Huang3, Ting-Chang Chang4, Chyong-Huey Lai4, Shih-Ming Jung5, Chuen Hsueh56 and Kwang-Huei Lin1*

Author Affiliations

1 Department of Biochemistry, Chang-Gung University, 259 Wen-hwa 1 Road, Taoyuan 333, Taiwan

2 Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan

3 Medical Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Republic of China

4 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan 333, Taiwan

5 Department of Pathology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

6 Pathology Core of Chang Gung Molecular Medicine Research Center, Chang-Gung University, Taoyuan 333, Taiwan

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BMC Cancer 2014, 14:555  doi:10.1186/1471-2407-14-555

Published: 1 August 2014



Cervical cancer continues to threaten women’s health worldwide, and the incidence of cervical adenocarcinoma (AD) is rising in the developed countries. Previously, we showed that glucose-regulated protein 58 (Grp58) served as an independent factor predictive of poor prognosis of patients with cervical AD. However, the molecular mechanism underlying the involvement of Grp58 in cervical carcinogenesis is currently unknown.


DNA microarray and enrichment analysis were used to identify the pathways disrupted by knockdown of Grp58 expression.


Among the pathway identified, the WNT signaling pathway was one of those that were significantly associated with knockdown of Grp58 expression in HeLa cells. Our experiments showed that β-catenin, a critical effector of WNT signaling, was stabilized thereby accumulated in stable Grp58 knockdown cells. Membrane localization of β-catenin was observed in Grp58 knockdown, but not control cells. Using a transwell assay, we found that accumulated β-catenin induced by Grp58 knockdown or lithium chloride treatment inhibited the migration ability of HeLa cells. Furthermore, an inverse expression pattern of Grp58 and β-catenin was observed in cervical tissues.


Our results demonstrate that β-catenin stability is negatively regulated by Grp58 in HeLa cells. Overexpression of Grp58 may be responsible for the loss of or decrease in membranous β-catenin expression in cervical AD.