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