Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells.

Gastric cancer is a highly aggressive tumor containing cancer stem cells (CSCs), which participate in tumor initiation, therapeutic resistance, and tumor relapse. Proline-rich protein 11 (PRR11) has been shown to be up-regulated in human cancers; however, its role in gastric CSCs is unknown. We hypothesize that PRR11 may affect tumorigenicity of gastric CSCs. In this study, we explored the biological function and regulation of PRR11 in gastric CSCs. Expression of PRR11 was evaluated in gastric CSC cell line by real-time quantitative PCR and western blot. The effect of PRR11 on tumorigenicity was examined by interference with gene expression using lentiviral vector-loaded shRNA. A xenograft tumor model using NOD/SCID mice was established to examine the role of PRR11 in tumor development. Data showed that PRR11 was highly expressed in gastric CSCs. PRR11 was responsible for the maintenance of self-renewal and tumorigenicity of gastric CSCs, and overexpression of exogenous PRR11 could restore the self-renewal of gastric non-CSCs. Furthermore, interference with PRR11 altered the expression of stemness transcription factors. Interestingly, MAPK signaling controlled PRR11 expression by increasing PRR11 protein stability, and maintained gastric CSCs self-renewal in a PRR11 dependent manner. PRR11 regulated self-renewal and tumorigenicity of gastric CSCs through MAPK signaling, and could be used as a therapeutic target for gastric cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

Citation

Hongtao Hu, Zongchang Song, Quanjun Yao, Xiang Geng, Li Jiang, Chenyang Guo, Hailiang Li. Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2018;47(4):1721-1728

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PMID: 30007956

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