Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma

Carboxylesterase 2a deletion provokes hepatic steatosis and insulin resistance in mice involving impaired diacylglycerol and lysophosphatidylcholine catabolism

“…[ 8 ] deliver several lines of evidence that Ces2a and CES2 play a critical role in liver microsomal DAG catabolism: i) Ces2a deficiency reduces microsomal DAG hydrolytic activity and significantly increases microsomal DAG levels in HFD-fed mice; ii) HFD-induced DAG accumulation in WT mice [ 8 ] and in Ces2a-ko mice could be reversed upon ectopic CES2 expression; iii) Pharmacological inhibition of CES2 enzymatic activity in HepG2 cells strongly reduced microsomal DAG hydrolytic activity paralleled by significantly increased sn -1,2 (2,3) DAG levels. In accordance, two recent studies linked low CES2 expression in cancer cell lines to DAG (and lysoPC) accumulation, which could be reversed upon CES2 overexpression, albeit these studies show a divergent impact of CES2 expression levels and the overall survival of cancer patients [ 21 , 22 ]. The stereochemical structure of DAGs determines their potential role in lipid synthesis and signaling processes.…”

“…Similarly, DGAT activity was also increased in Ces2a-ko microsomal liver fraction ( Figure 4 G) although Dgat1 and Dgat2 gene expression was comparable between the genotypes ( Figure 4 D). A recent study demonstrated a negative correlation of CES2 expression and intracellular lysophosphatidylcholine (lysoPC) and DAG levels [ 21 , 22 ] in cancer cell lines and another study discovered lysoPC (16:0) as a PPARg ligand [ 23 ]. Hence Ces2a deficiency may impact lysoPC levels as well.…”

“…Interestingly, elevated lysoPC levels have been demonstrated in NASH patients and functionally linked to hepatocyte stress, lipo-apoptosis and insulin resistance [ [36] , [37] , [38] ]. Moreover, two recent studies associated low CES2 expression to lysoPC accumulation in human cancer cell lines [ 21 , 22 ]. However, in these studies, no hydrolytic activities were investigated, and the authors speculated that CES2 hydrolyzes PC and other phospholipids leading to lysoPC accumulation.…”

BST2 regulated by the transcription factor STAT1 can promote metastasis, invasion and proliferation of oral squamous cell carcinoma via the AKT/ERK1/2 signaling pathway

“…OSCC is a malignant tumor with high morbidity and mortality and is a threat to human health (16). OSCC often involves the tongue and lips, and can easily spread to other organs, including the lungs and lymph nodes (17)(18)(19). The lack of specific detection of OSCC tumor boundaries makes it difficult to determine the extent of disease at the time of treatment and often adversely affects a patient's appearance and quality of life after surgery (20).…”

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…176 It is therefore of no surprise with its known lipid dysregulation and urgency that oncology was the biggest application area in 2022, where the following cancers were studied: bladder, 177 brain, 155 breast, [178][179][180][181][182] colorectal, [183][184][185][186][187][188] endometrial, 189 gallbladder, 190 gastric, 191 kidney, 192 liver, [193][194][195][196][197] lungs, 156,[198][199][200] nasopharyngeal, 201 ovarian, 202 paediatric, 203 prostate, 204,205 and skin. 206 To maximize the survival rates of cancer patients, it is important to identify cancer at its early stages, where tumours can be surgically removed or treated with milder drug regimens. 207 The average 5-year survival rate in the early stages is 91%; whereas, the average 5-year survival rate in the late stages is 26%.…”