Psoriasin overexpression confers drug resistance to cisplatin by activating ERK in gastric cancer

Li,Liting; Cui,Yuxin; Ye,Lin; Zhao,Zehang; Jiang,Wen  G.; Ji,Jiafu

doi:10.3892/ijo.2018.4455

Psoriasin overexpression confers drug resistance to cisplatin by activating ERK in gastric cancer

Authors:
- Liting Li
- Yuxin Cui
- Lin Ye
- Zehang Zhao
- Wen G. Jiang
- Jiafu Ji
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Affiliations: Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Peking University, Beijing 100142, P.R. China, Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK
Published online on: June 26, 2018 https://doi.org/10.3892/ijo.2018.4455
Pages: 1171-1182

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Abstract

Psoriasin, a member of the S100 multigenic family, which is aberrantly expressed in a variety of human tumors, is considered as an attractive molecular target for cancer treatment. The present study aimed to characterize the role of psoriasin in gastric cancer (GC), the associated pathways through which it contributes to cancer development and progression, and the effect of psoriasin on cellular response to pre-operative chemotherapy in patients with GC. Expression of psoriasin mRNA and protein were analyzed using quantitative polymerase chain reaction and immunohistochemistry of gastric cancer cohorts, respectively. Gastric cancer cell models with differential expression of psoriasin were generated using stable cell lines that overexpressed psoriasin. The in vitro biological functions of the cells in response to psoriasin overexpression and to chemotherapeutic agents were assessed using various cell-based assays. Psoriasin was overexpressed in patients with advanced GC, and high psoriasin levels led to poor clinical outcomes. Increasing psoriasin expression in GC cell lines promoted cell proliferation, migration and invasion in vitro. Furthermore, psoriasin overexpression caused alterations in the levels of epithelial-mesenchymal transition-associated proteins, and activated the extracellular signal-regulated kinase signaling pathway. Additionally, higher levels of psoriasin expression were significantly associated a lack of response to neoadjuvant chemotherapy in patients with GC. Psoriasin overexpression tended to decrease the sensitivity of GC cells to cisplatin, potentially by inhibiting apoptosis or increasing the S-phase population. Taken together, these results indicate that psoriasin may be a promising therapeutic target for GC treatment, and a potential molecular marker to predict patient response to pre-operative chemotherapy.

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