High expression of LPCAT1 promotes oral squamous cell carcinoma progression via activation of platelet activating factor/platelet activating factor receptor pathway

Background:The relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown.We investigated LPCAT1 expression and its functional mechanism in OSCCs. Methods:We analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines.Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status.We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression. Results:LPCAT1 mRNA and protein were up-regulated significantly (p<0.05) in OSCC-derived cell lines compared with human normal oral keratinocytes.Immunohistochemistry showed significantly (p<0.05)elevated LPCAT1 expression in primary OSCCs compared with normal counterparts and a strong correlation between LPCAT1-positive OSCCs and tumoral size and regional lymph node metastasis.In LPCAT1 knockdown cells, cellular proliferation and invasiveness decreased significantly (p<0.05);cellular migration was inhibited compared with control cells.Down-regulation of LPCAT1 resulted in a decreased intercellular PAF concentration and PAFR expression. Conclusion:LPCAT1 was overexpressed in OSCCs and correlated with cellular invasiveness and migration.LPCAT1 may contribute to tumoral growth and metastasis in oral cancer.