Lysophosphatidylcholine inhibits lung cancer cell proliferation by regulating fatty acid metabolism enzyme long‐chain acyl‐coenzyme A synthase 5

Abstract

Lung cancer is a widespread malignancy with a high death rate and disorder of lipid metabolism. Lysophosphatidylcholine (lysoPC) has anti-tumour effects, although the underlying mechanism is not entirely known. The purpose of this study aims at defining changes in lysoPC in lung cancer patients, the effects of lysoPC on lung cancer cells and molecular mechanisms. Lung cancer cell sensitivity to lysoPC was evaluated and decisive roles of long-chain acyl-coenzyme A synthase 5 (ACSL5) in lysoPC regulation were defined by comprehensively evaluating transcriptomic changes of ACSL5-downregulated epithelia. ACSL5 over-expressed in ciliated, club and Goblet cells in lung cancer patients, different from other lung diseases. LysoPC inhibited lung cancer cell proliferation, by inducing mitochondrial dysfunction, altering lipid metabolisms, increasing fatty acid oxidation and reprograming ACSL5/phosphoinositide 3-kinase/extracellular signal-regulated kinase-regulated triacylglycerol-lysoPC balance. Thus, this study provides a general new basis for the discovery of reprogramming metabolisms and metabolites as a new strategy of lung cancer precision medicine.

Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma

“…33 However, in a contrasting role, it has also demonstrated antitumor effects in lung cancer cells through the regulation of the fatty acid metabolism enzyme, long-chain acyl-coenzyme A synthase 5. 34 Light drinking as well as moderate to heavy alcohol consumption significantly increased the risks of the gastrointestinal cancers than those who remained a non-drinker in a dose dependent manner, including to esophageal cancer, gastric cancer, and colorectal cancer. 35 And the main mechanism is likely related to the primary metabolites, acetaldehydes, that have a local toxic effect that increases the risk.…”

“…Similar to glycoursodeoxycholic acid, LysoPC(14:0) is a known inducer of lymphocyte and macrophage migration, pro‐inflammatory cytokine production, oxidative stress, and apoptosis, contributing to the exacerbation of inflammation and disease progression 33 . However, in a contrasting role, it has also demonstrated antitumor effects in lung cancer cells through the regulation of the fatty acid metabolism enzyme, long‐chain acyl‐coenzyme A synthase 5 34 …”

Roles of glutamic pyruvate transaminase 2 in reprogramming of airway epithelial lipidomic and metabolomic profiles after smoking

“…Altered lipids in plasma, including phospholipids, sphingolipids, glycerides, and cholesteryl esters, were suggested for early diagnosis, monitoring, and prognosis of acute exacerbation of COPD or stable COPD 29,37,38 . The combination of lipidomics with clinical phenomics enables to determine disease severity, disease course, staging, subtype treatment and prognosis 23,39–41 .…”

“…This study integrated circulating metabolomics and lipidomics and found that elevated levels of glutamate and glutamate‐associated pathways were accompanied by obvious alterations of lipid element levels in COPD patients. Cigarette smoking is the dominant factor in the pathogenesis of COPD, 42 associated with cellular lipid metabolism, leading to the accumulation of the cytotoxic lipid CER in lung epithelial cells 37,43 . We examined changes in metabolic and lipidomic profiles in CSE‐stimulated airway epithelial cells and found activation of glutamate and glutamate‐associated pathways and regulatory roles of GPT2 in smoking‐induced metabolism reprogramming.…”

“…Altered lipids in plasma, including phospholipids, sphingolipids, glycerides, and cholesteryl esters, were suggested for early diagnosis, monitoring, and prognosis of acute exacerbation of COPD or stable COPD. 29 , 37 , 38 The combination of lipidomics with clinical phenomics enables to determine disease severity, disease course, staging, subtype treatment and prognosis. 23 , 39 , 40 , 41 This study integrated circulating metabolomics and lipidomics and found that elevated levels of glutamate and glutamate‐associated pathways were accompanied by obvious alterations of lipid element levels in COPD patients.…”