J Cancer 2020; 11(9):2667-2678. doi:10.7150/jca.40955 This issue

Research Paper

CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR

Yiting Sun1,2*, Song Li1*, Wenbin Yu3*, Cheng Chen3, Teng Liu3, Lanbo Li4, Di Zhang1, Zeyi Zhao1, Jing Gao1, Xiao Wang5, Duanbo Shi6, Lian Liu1✉

1. Department of Medical Oncology, Cancer Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China;
2. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China;
3. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China;
4. Animal Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China;
5. Department of Pathology, School of Medicine, Shandong University, Jinan, Shandong, 250012, China;
6. Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Sun Y, Li S, Yu W, Chen C, Liu T, Li L, Zhang D, Zhao Z, Gao J, Wang X, Shi D, Liu L. CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR. J Cancer 2020; 11(9):2667-2678. doi:10.7150/jca.40955. Available from https://www.jcancer.org/v11p2667.htm

File import instruction

Abstract

CD148 is a member of the receptor-type protein tyrosine phosphatase family encoded by the PTPRJ gene and has controversial impacts on cancers. In this study, we investigated the clinical significance of CD148 in gastric cancer and the possible mechanisms. Suppressed CD148 expression indicated adverse pathological features and poor outcomes in gastric cancer patients. CD148 overexpression impeded tumor proliferation, motility, and invasiveness, while CD148 knock-down or knockout promoted the ability of gastric cancer cells to grow and metastasize in vitro and in vivo. Mechanistically, CD148 negatively regulated EGFR phosphorylation of multiple tyrosine residues, including Y1173, Y1068, and Y1092, and remarkably inhibited downstream PI3K/AKT and MEK/ERK pathways. In silico analysis revealed that gene deletions or missense/truncated mutations of PTPRJ gene rarely occurred in gastric cancers. Instead, a 3' UTR-specific methylation might regulate CD148 expression, and the potential regulators were TET2 and TET3. Collectively, our results suggest that CD148 is a convincing prognostic marker as well as a potential therapeutic target for gastric cancer.

Keywords: gastric cancer, CD148, epidermal growth factor receptor, protein tyrosine phosphatase