Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis

EBioMedicine
Zhiyuan TangHaiping Hao

Abstract

Tumor cells display metabolic changes that correlate with malignancy, including an elevated hydrolysis of monoacylglycerol (MAG) in various cancer types. However, evidence is absent for the relationship between MAG lipolysis and NSCLC. MAG hydrolase activity assay, migration, invasion, proliferation, lipids quantification, and transactivation assays were performed in vitro. Tumor xenograft studies and lung metastasis assays were examined in vivo. The correlations of MAGL/ABHD6 expression in cancerous tissues with the clinicopathological characteristics and survival of NSCLC patients were validated. ABHD6 functions as the primary MAG lipase and an oncogene in NSCLC. MAG hydrolase activities were more than 11-fold higher in cancerous lung tissues than in paired non-cancerous tissues derived from NSCLC patients. ABHD6, instead of MAGL, was significantly associated with advanced tumor node metastasis (TNM) stage (HR, 1.382; P = 0.004) and had a negative impact on the overall survival of NSCLC patients (P = 0.001). ABHD6 silencing reduced migration and invasion of NSCLC cells in vitro as well as metastatic seeding and tumor growth in vivo. Conversely, ectopic overexpression of ABHD6 provoked the pathogenic potential. ABHD6 blockade ...Continue Reading

Citations

Jan 15, 2021·British Journal of Pharmacology·Cristina MiralpeixRosalía Rodríguez-Rodríguez
Jan 9, 2021·Cancer & Metabolism·Shilpa R NagarajanAndrew J Hoy
Feb 6, 2021·International Journal of Molecular Sciences·Gabriele GrasmannKatharina Leithner
Apr 24, 2021·Journal of Pharmaceutical and Biomedical Analysis·Jing YuHonghao Zhou
Jul 3, 2021·Journal of Medicinal Chemistry·Giulia BononiCarlotta Granchi

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Datasets Mentioned

BETA
AM630
T0070907

Methods Mentioned

BETA
transfection
protein assay
xenograft
PCR

Software Mentioned

QuanLynx applications manager
file

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