Lysophosphatidylcholine Acyltransferase1 Overexpression Promotes Oral Squamous Cell Carcinoma Progression via Enhanced Biosynthesis of Platelet-Activating Factor

Shida-Sakazume, Tomomi; Endo‐Sakamoto, Yosuke; Unozawa, Motoharu; Fukumoto, Chonji; Shimada, Ken; Kasamatsu, Atsushi; Ogawara, Katsunori; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

doi:10.1371/journal.pone.0120143

Cited by 44 publications

(39 citation statements)

References 40 publications

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“…PC and LPC 16:0 levels were higher and lower, respectively, in gastric cancer tissues of such patients [ 31 ]. LPCAT1 overexpression has been noted in many other types of cancer including breast [ 36 ] and colorectal [ 37 ] cancers, and the level has often been considered clinically relevant in tumorigenesis [ 31 , 36 , 38 – 40 ].…”

Section: Discussionmentioning

confidence: 99%

Reduced levels of N’-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine 16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the correlation with recurrence-free survival

et al. 2017

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We searched for metabolic biomarkers that may predict the prognosis of patients with intrahepatic cholangiocarcinoma (IHCC). To this end, a total of 237 serum samples were obtained from IHCC patients (n = 87) and healthy controls (n = 150), and serum metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two stratified algorithms were used to select the metabolites, the levels of which predicted the prognosis of IHCC patients. We performed MS/MS and multiple-reaction-monitoring MS analyses to identify and quantify the selected metabolites. Continuous biomarker levels were dichotomized based on cutoffs that maximized between-group differences in recurrence-free survival (RFS) in terms of the log-rank test statistic. These RFS differences were analyzed using the log-rank test, and survival curves were drawn with the aid of the Kaplan–Meier method. Six metabolites (l-glutamine, lysophosphatidylcholine [LPC] 16:0, LPC 18:0, N’-methyl-2-pyridone-5-carboxamide [2PY], fibrinopeptide A [FPA] and uric acid) were identified as candidate metabolic biomarkers for predicting the prognosis of IHCC patients. Of these metabolites, levels of l-glutamine, uric acid, LPC 16:0, and LPC 18:0 were significantly lower in the serum from IHCC patients, whereas levels of 2PY and FPA were significantly higher (p < 0.01). 2PY and LPC 16:0 showed significantly better RFS at low level than high level (2PY, median RFS: 15.16 months vs. 5.90 months, p = 0.037; LPC 16:0, median RFS: 15.62 months vs. 9.83 months, p = 0.035). The findings of this study suggest that 2PY and LPC 16:0 identified by metabolome-based approaches may be useful biomarkers for IHCC patients.

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Section: Discussionmentioning

confidence: 99%

Reduced levels of N’-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine 16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the correlation with recurrence-free survival

et al. 2017

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“…For example, the PAF basic biosynthetic enzymes such as LPCAT1 (an isoform of lyso-PAF-AT) are overexpressed in several cancer cells and correlated with cellular invasiveness and migration. Therefore, LPCAT1 seems to contribute to tumour growth and metastasis in these types of cancer [ 176 , 177 ]. Moreover, endothelial cell PAF production results in enhanced inflammatory cell recruitment, while endothelial accumulation of PAF by PAF production and inactivation of PAF-AH plays also a role in cancer cell migration to distal locations [ 178 ].…”

Section: The Role Of Paf In Chronic Diseases and The Beneficial Efmentioning

confidence: 99%

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

2018

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Since the Seven Countries Study, dietary cholesterol and the levels of serum cholesterol in relation to the development of chronic diseases have been somewhat demonised. However, the principles of the Mediterranean diet and relevant data linked to the examples of people living in the five blue zones demonstrate that the key to longevity and the prevention of chronic disease development is not the reduction of dietary or serum cholesterol but the control of systemic inflammation. In this review, we present all the relevant data that supports the view that it is inflammation induced by several factors, such as platelet-activating factor (PAF), that leads to the onset of cardiovascular diseases (CVD) rather than serum cholesterol. The key to reducing the incidence of CVD is to control the activities of PAF and other inflammatory mediators via diet, exercise, and healthy lifestyle choices. The relevant studies and data supporting these views are discussed in this review.

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“…In addition, other LPCATs have also been demonstrated to contribute to tumor development in various tissues. Upregulation of LPCAT1 has been observed in multiple tumors, including clear renal cell carcinoma (150), oral squamous cell carcinoma (151), hepatoma (152), as well as esophageal (153), gastric (154), breast (155), colorectal (156), and prostate cancers (157)(158)(159). LPCAT1 expression correlates with the prognosis and survival in several tumors (150,155,157,158) and may be used as a diagnostic marker in others (153,157).…”

Section: Lpcats In Cancermentioning

confidence: 99%

Phospholipid Remodeling in Physiology and Disease

Wang

Tontonoz

2019

Annu. Rev. Physiol.

328

240

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Phospholipids are major constituents of biological membranes. The fatty acyl chain composition of phospholipids determines the biophysical properties of membranes and thereby affects their impact on biological processes. The composition of fatty acyl chains is also actively regulated through a deacylation and reacylation pathway called Lands’ cycle. Recent studies of mouse genetic models have demonstrated that lysophosphatidylcholine acyltransferases (LPCATs), which catalyze the incorporation of fatty acyl chains into the sn-2 site of phosphatidylcholine, play important roles in pathophysiology. Two LPCAT family members, LPCAT1 and LPCAT3, have been particularly well studied. LPCAT1 is crucial for proper lung function due to its role in pulmonary surfactant biosynthesis. LPCAT3 maintains systemic lipid homeostasis by regulating lipid absorption in intestine, lipoprotein secretion, and de novo lipogenesis in liver. Mounting evidence also suggests that changes in LPCAT activity may be potentially involved in pathological conditions, including nonalcoholic fatty liver disease, atherosclerosis, viral infections, and cancer. Pharmacological manipulation of LPCAT activity and membrane phospholipid composition may provide new therapeutic options for these conditions.

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Lysophosphatidylcholine Acyltransferase1 Overexpression Promotes Oral Squamous Cell Carcinoma Progression via Enhanced Biosynthesis of Platelet-Activating Factor

Cited by 44 publications

References 40 publications

Reduced levels of N’-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine 16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the correlation with recurrence-free survival

Reduced levels of N’-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine 16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the correlation with recurrence-free survival

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

Phospholipid Remodeling in Physiology and Disease

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