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Sphingosine kinase 1 is upregulated with lysophosphatidic acid receptor 2 in human colorectal cancer

World Journal of Gastroenterology 2016年第8期22卷 2503-2511页

作者： Dai Shida Satoru Inoue Yuki Yoshida Atsushi Kodaka Tsutomu Tsuji Makoto Tsuiji Colorectal Surgery Division National Cancer Center Hospital Department of Surgery Tokyo Metropolitan Bokutoh Hospital Department of Microbiology Hoshi University School of Pharmaceutical Sciences

AIM: To examine the expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid (LPA) receptor overexpressed in various cancers, in human colorectal ***: Real-time reverse-transcription polymerase chain reaction was used to measure the mRNA expression of SphK1, LPAR2, and the three major S1P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of SphK1 and ***: Colorectal cancer tissue in 22 of 27 patients had higher levels of SphK1 mRNA than in normal tissue. In two-thirds of the samples, SphK1 mRNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 mRNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between SphK1 and LPAR2 expression [Pearson’s correlation coefficient (r) = 0.784 and P < 0.01]. The mRNA levels of SphK1 and LPAR2 did not correlate with TNM ***: Our findings suggest that S1P and LPA may play important roles in the development of colorectal cancer via the upregulation of SphK1 and LPAR2, both of which could serve as new therapeutic targets in the treatment of colorectal cancer.

关键词： Sphingosine kinase 1 lysophosphatidic acid receptor 2 Carcinogenesis Colorectal cancer Sphingosine 1-phosphate

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