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SPNS 2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway
Author(s) -
Gu Xinyue,
Jiang Yang,
Xue Weinan,
Song Chengxin,
Wang Yangyang,
Liu Yanlong,
Cui Binbin
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13124
Subject(s) - protein kinase b , mapk/erk pathway , s1pr1 , cancer research , apoptosis , pi3k/akt/mtor pathway , colorectal cancer , sphingosine 1 phosphate , cancer cell , chemistry , cancer , signal transduction , biology , microbiology and biotechnology , medicine , sphingosine , receptor , biochemistry , vascular endothelial growth factor a , vascular endothelial growth factor , vegf receptors
Colorectal cancer ( CRC ) is a prevalent malignant tumour that causes considerable cancer‐related deaths globally. The sphingolipid transporter 2 ( SPNS 2), a sphingosine‐1‐phosphate (S1P) transporter, modulates multiple biological events including malignancy of cancer cells. In this study, the effects of SPNS 2 on CRC progression were studied. We found that SPNS 2 expression was significantly upregulated in CRC tissues compared to that in adjacent non‐tumour tissues. To assess the role of SPNS 2 in CRC cells, we performed loss‐ and gain‐of‐function experiments in SW 480 and HCT 116 cells, respectively. The results demonstrated that SPNS 2 promoted proliferation, migration and invasion, and inhibited apoptosis in CRC cells. Additionally, SPNS 2 enhanced the release of intracellular S1P, and increased S1P receptor 1 (S1 PR 1) and S1 PR 3 expression. Moreover, SPNS 2 activated the Akt and ERK pathways, and the biological behaviours of SPNS 2 were attenuated by Akt or ERK inhibitor in HCT 116 cells. In conclusion, our results demonstrated that SPNS 2 promoted proliferation, migration and invasion, and inhibited apoptosis by regulating S1P/S1 PR 1/3 axis and activating Akt and ERK pathway in CRC cells.