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Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis
- Source :
- EBioMedicine, EBioMedicine, Vol 53, Iss, Pp-(2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Background: 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. Methods: 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. Findings: 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 significantly induced intracellular MAG accumulation which activated PPARα/γ signaling and inhibited cancer pathophysiology. Interpretation: The present study provide evidence for a previously uncovered pro-oncogenic function of ABHD6 in NSCLC, with the outlined metabolic mechanisms shedding light on new potential strategies for anticancer therapy. Fund: This work was supported by the Project for Major New Drug Innovation and Development (2015ZX09501010 and 2018ZX09711001-002-003). Keywords: NSCLC, ABHD6, Aggressiveness, MAG
- Subjects :
- 0301 basic medicine
Adult
Male
Research paper
Lung Neoplasms
Lipolysis
lcsh:Medicine
Mice, Nude
Mice, SCID
Malignancy
NSCLC
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Transactivation
Mice
0302 clinical medicine
Aggressiveness
In vivo
Carcinoma, Non-Small-Cell Lung
medicine
Gene silencing
Animals
Humans
Aged
Aged, 80 and over
lcsh:R5-920
Mice, Inbred BALB C
Oncogene
business.industry
lcsh:R
Cancer
General Medicine
Middle Aged
medicine.disease
ABHD6
MAG
Monoacylglycerol Lipases
respiratory tract diseases
3. Good health
Monoacylglycerol lipase
030104 developmental biology
A549 Cells
030220 oncology & carcinogenesis
Cancer research
Monoglycerides
Female
lcsh:Medicine (General)
business
Subjects
Details
- Language :
- English
- ISSN :
- 23523964 and 09501010
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....d35f97804f558ea8cb7bf8fb7c07e0c5