Protein tyrosine phosphatase receptor S acts as a... : Hepatology (original) (raw)

Hepatobiliary Malignancies

Protein tyrosine phosphatase receptor S acts as a metastatic suppressor in hepatocellular carcinoma by control of epithermal growth factor receptor–induced epithelial‐mesenchymal transition

Wang, Zhi‐Chao1,†; Gao, Qiang1,†; Shi, Jie‐Yi1,†; Guo, Wei‐Jie2,†; Yang, Liu‐Xiao1,†; Liu, Xin‐Yang3,†; Liu, Long‐Zi1; Ma, Li‐Jie1; Duan, Meng1; Zhao, Ying‐Jun3; Wu, Yong‐Na4; Gao, Dong‐Mei1; Wang, Xiao‐Ying1; Shi, Guo‐Ming1; Ding, Zhen‐Bin1; Ke, Ai‐Wu1; Tang, Qi‐Qun5; Cao, Ya6; Zhou, Jian1,7; Fan, Jia*,1,7

1Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan UniversityShanghaiChina

2Shanghai Medical College, Fudan UniversityShanghaiChina

3Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan UniversityShanghaiChina

4Department of General Surgerythe First Hospital of Lanzhou UniversityLanzhouChina

5Key Laboratory of Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular BiologyFudan University Shanghai Medical CollegeShanghaiChina

6Cancer Research Institute, Key Laboratory of Chinese Ministry of Education, Xiangya School of Medicine, Central South UniversityChangshaChina

7Institute of Biomedical Sciences, Fudan UniversityShanghaiChina

*Address reprint requests to: Jia Fan, M.D., Ph.D., Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, 180 Fenglin Road, Shanghai 200032, China. E‐mail: [email protected]; fax: +86‐21‐64037181.

†These authors contributed equally to this work.

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Errata

Abstract

Hepatocellular carcinoma (HCC) is the third‐most lethal cancer worldwide. Understanding the molecular pathogenesis of HCC recurrence and metastasis is the key to improve patients’ prognosis. In this study, we report that protein tyrosine phosphatase receptor S (PTPRS) is significantly down‐regulated in nearly 80% of HCCs, and its expression negatively correlates with aggressive pathological features, such as larger tumor size and advanced stage. In addition, PTPRS deficiency is independently associated with shorter survival and increased recurrence in patients, although 16.7% of HCCs show intratumor heterogeneous expression of PTPRS. Restoration of wild‐type, but not mutant, PTPRS expression significantly inhibits HCC cell migration and invasion in vitro as well as lung metastasis in vivo, whereas knockdown of its expression significantly promotes invasion and metastasis. Notably, PTPRS‐regulated HCC invasiveness is accompanied by typical changes of epithelial‐mesenchymal transition (EMT). Moreover, PTPRS forms a complex with epithermal growth factor receptor (EGFR) and regulates its tyrosine residues’ phosphorylation. Ectopic expression of EGFR reverses the metastasis‐inhibiting effects of PTPRS, whereas silencing of EGFR or inhibiting phosphorylation of key molecules in EGFR downstream pathways reinhibits EMT and metastasis caused by PTPRS down‐regulation. Meanwhile, promoter hypermethylation of PTPRS is frequently detected in HCC samples and cell lines. Treatment with a demethylation agent, 5‐aza‐2′‐deoxycytidine, recovers PTPRS expression in a dose‐dependent manner. Conclusions: Epigenetic inactivation of PTPRS may increase phosphorylation and activity of EGFR signaling to promote EMT and metastasis in HCC. (Hepatology 2015;62:1201‐1214)

Errata

During manuscript preparation and revision for the article by Zhichao W et al, a wrong western blot panel was placed in Figure 3D. Specifically, the western blot image of p-FAK (Tyr397) in HCCLM3 cells, shown on the right panel of Figure 3D, was incorrect. After careful verification of the original data, the corrected Figure 3D is now shown below. We declare that the replacement data comes from the original data. The authors sincerely apologize for this error and any inconvenience caused to our readers. All authors agree with this correction, and state that this correction does not affect the conclusions of the article.

Hepatology. 81(4):E131-E132, April 2025.

In the October 2015 issue of Hepatology, in the article titled “Protein Tyrosine Phosphatase Receptor S Acts as a Metastatic Suppressor in Hepatocellular Carcinoma by Control of Epithermal Growth Factor Receptor–Induced Epithelial‐Mesenchymal Transition” (volume 62, pages 1201‐1214; doi: 10.1002/hep.27911), by Zhi‐Chao Wang, Qiang Gao, Jie‐Yi Shi, Wei‐Jie Guo, Liu‐Xiao Yang, Xin‐Yang Liu, Long‐Zi Liu, Li‐Jie Ma, Meng Duan, Ying‐Jun Zhao, Yong‐Na Wu, Dong‐Mei Gao, Xiao‐Ying Wang, Guo‐Ming Shi, Zhen‐Bin Ding, Ai‐Wu Ke, Qi‐Qun Tang, Ya Cao, Jian Zhou and Jia Fan, the word “Epithermal” in the title should have read “Epidermal.”

We apologize for this error.

Hepatology. 63(1):349, January 2016.