Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis

doi:10.1007/s11684-021-0830-0

Front. Med.

2021, Vol. 15

Issue (5) : 649-656 https://doi.org/10.1007/s11684-021-0830-0

REVIEW

Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis

Jingyue Zhang, Yawen Song, Qianqian Shi, Li Fu(

)

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical university, Ministry of Education, Tianjin 300060, China

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Abstract

Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism, which is manifested by increased endogenous fat mobilization, hypertriglyceridemia, and increased fatty acid synthesis. Fatty acid synthase (FASN) is a key enzyme for the de novo synthesis of fatty acids, and monoacylglycerol esterase (MGLL) is an important metabolic enzyme that converts triglycerides into free fatty acids. Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways, the most common of which is the PI3K–AKT signaling pathway. They can also regulate the immune microenvironment, participate in epithelial–mesenchymal transition, and then regulate tumor invasion and metastasis. Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion. This article introduces the structures and functions of FASN and MGLL, their relationship with abnormal lipid metabolism, and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.

Keywords FASN MGLL lipid metabolism tumor invasion metastasis

Corresponding Author(s): Li Fu

Online First Date: 14 May 2021 Issue Date: 01 November 2021

Cite this article:

Jingyue Zhang,Yawen Song,Qianqian Shi, et al. Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis[J]. Front. Med., 2021, 15(5): 649-656.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0830-0
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I5/649

Fig.1 Cellular metabolism process involving FASN and MGLL.

Fig.2 PI3K–AKT pathway. RTK will create binding sites that recruit the lipid kinase phosphatidylinositol 3-kinase (PI3K) to the plasma membrane. Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) is the main phosphoinositide at the cell membrane. PI3K phosphorylates PIP2 and yields PI 3,4,5-triphosphate (PIP3). Phosphatase and tensin homolog (PTEN) counteracts the action of PI3K by dephosphorylating PIP3 to PIP2. PIP3 acts as a second messenger to recruit the serine/threonine protein kinase AKT to the plasma membrane, where it is fully activated by phosphoinositide-dependent protein kinase 1 (PDPK1) and the mechanistic target of rapamycin complex 2 (mTORC2). AKT signal transduction promotes cell survival, growth, and proliferation in part by inducing various changes in cell metabolism.

Tab.1 Expression and function of FASN and MGLL in different tumor types

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