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Apolipoprotein M (ApoM) is a sphingosine 1-phosphate (S1P) carrier involved in the regulation of S1P. Signaling pathways involving sphingosine kinases (SphKs) and S1P-S1P receptors (S1PRs) play important roles in the oncogenesis of multiple cancers including non-small cell lung cancer (NSCLC). In the present study we have clarified the potential roles of ApoM on the oncogenesis process of NSCLC cells. We detected the ApoM expression in NSCLC tissues and further analyzed its clinical significance. Moreover, we determined effects of ApoM overexpression on tumor cellular behaviours of NSCLC in vitro and in vivo. Our results demonstrated that ApoM protein mass were clearly higher in the NSCLC tissues than in non-NSCLS tissues. Overexpression of ApoM could promote NSCLC cell proliferation and invasion in vitro and tumor growth in vivo, which might be via upregulating S1PR1 and activating the ERK1/2 and PI3K/AKT signaling pathways. It is concluded that up-regulation of ApoM in NSCLC might be associated with the tumor induced inflammation and tumor microenvironment as well as promoting oncogenesis of NSCLC. Further study needs to elucidate the underlying mechanisms., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Autophagy is thought to be a key mechanism in maintaining the balance of liver lipid metabolism. However, the relationship between apolipoprotein M (ApoM) and autophagy has not been reported, and the role of ApoM in triglyceride metabolism is still unclear. In this study, we investigated the correlation between ApoM and autophagy and liver triglyceride metabolism in ApoM-knockout animal and cellular models. First, we observed that spontaneous hepatic steatosis developed in the liver of adult ApoM -/- mice, which was presented as the accumulation of large quantities of lipid droplets in hepatocytes under electron microscopy; Oil Red O staining showed significant accumulation of triglycerides. At the molecular level, the expression of lipid synthesis-associated proteins (primarily triglyceride synthesis) as well as acetyl-CoA carboxylase alpha (ACACA), fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBP1) was upregulated. Moreover, lipid metabolic disorder and accumulation were accompanied by dysfunction in autophagy, which displayed predominantly as inhibition of the degradation pathway; for example, P62 protein accumulated and key proteins involved in the initiation of autophagy including ATG7, ATG5-12, Beclin1 and the LC3BII/LC3BI ratio were upregulated as a feedback response. When the autophagy dysfunction was ameliorated by the activation of autophagy pathways induced by starvation, the lipid metabolic disorder was corrected to a certain extent. This suggests that the autophagy dysfunction caused by the deficiency of ApoM is an important factor in hepatic steatosis (triglyceride accumulation). ApoM plays a key role in normal autophagy activity in the liver and thereby further regulates the metabolism of liver lipids, particularly triglycerides., (Copyright © 2017. Published by Elsevier Inc.)