Metallopanstimulin-1 regulates invasion and migration of gastric cancer cells partially through integrin β4

• Published in: Carcinogenesis (New York) Vol. 34; no. 12; pp. 2851 - 2860
• Main Authors: Yang, Zhong-Yin, Jiang, He, Qu, Ying, Wei, Min, Yan, Min, Zhu, Zheng-Gang, Liu, Bing-Ya, Chen, Guo-Qiang, Wu, Ying-Li, Gu, Qin-Long
• Format: Journal Article
• Language: English
• Published: England 01.12.2013
• Subjects: Adult; Aged; Aged, 80 and over; Cell Line; Cell Line, Tumor; Cell Movement - genetics; Down-Regulation - genetics; Female; Gene Expression Regulation, Neoplastic - genetics; Humans; Integrin beta4 - genetics; Integrin beta4 - metabolism; Male; Metalloproteins - genetics; Metalloproteins - metabolism; Middle Aged; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgt226

MPS-1 (metallopanstimulin-1), also known as ribosomal protein S27, was overexpressed in gastric cancer cells. However, how MPS-1 contributes to gastric carcinogenesis has not been well characterized. Here, we show that high expression of MPS-1 was observed in gastric cancer tissues and associated with gastric cancer cell metastasis. Alteration of MPS-1 expression regulates invasion and migration of gastric cancer cells both in vitro and in vivo. Furthermore, by using Signal-Net and cluster analyses of microarray data we identified integrin β4 (ITGB4) as a downstream target of MPS-1 that mediates its effects on cell metastasis. Knockdown of MPS-1 expression in gastric cancer cells led to significant reduction of ITGB4 expression at both the RNA and protein levels. Mechanically, we found that overexpression of ITGB4 in MPS-1 knockdown cells largely recovers the ability of invasion and migration. Conversely, knockdown of ITGB4 partially reduced cell invading/migrating ability induced by MPS-1 overexpression. Moreover, MPS-1 and ITGB4 expressions are positively correlated in gastric cancer cell lines and tissues. Finally, the survival analyses show that the expression of MPS-1 and ITGB4 is associated with poor outcomes in gastric cancer patients. Collectively, our findings suggest that MPS-1 regulates cell invasiveness and migration partially through ITGB4 and that MPS-1/ITGB4 signaling axis may serve as therapeutic targets in the treatment of gastric cancer.