The role of acetyl-coA carboxylase2 in head and neck squamous cell carcinoma

Abstract

Background Acetyl-CoA carboxylase (ACC) plays an important role in the metabolism of various cancer cells, but its role in head and neck squamous cell carcinoma (HNSCC) is uncertain. Therefore, in the present study, we explored the role of ACC2 in HNSCC. Methods Western blot and immunohistochemistry assays were used to determine ACC2 protein expression levels in laryngocarcinoma and adjacent normal tissues derived from patients with laryngocarcinoma. ACC2 expression was knocked down in the hypopharyngeal cancer cell line FaDu to determine its effect on apoptosis. Lipid oil red staining was used to test the change of intracellular lipid. Results The results showed that the ACC2 protein was highly expressed in laryngocarcinoma and that the ACC2 expression level was positively associated with the clinical cancer stage and negatively associated with the degree of laryngocarcinoma cell differentiation. Kaplan–Meier analyses indicated that compared with patients having low levels of ACC2, those with high ACC2 levels had a decreased 5-year survival rate. The results of western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that knockdown of ACC2 accelerated apoptosis in FaDu cells. Furthermore, knockdown of ACC2 significantly reduced the intracellular lipid levels in FaDu cells. Conclusion These findings suggest that ACC2 may be an important prognostic marker for patients with HNSCC and that ACC2 may be a potential target in the treatment of HNSCC.

Lipid metabolism and cancer

“…ACC2 protein is highly expressed in laryngocarcinoma, and ACC2 expression level is positively associated with clinical cancer stage and a decreased 5-yr survival rate ( Li et al, 2019a ). During nutrient abundance, prolyl hydroxylase domain protein 3 (PHD3) hydroxylates and activates ACC2, thereby repressing FAO.…”

Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

“…The link between the lipid metabolism associated molecules and neoplastic phenotypic changes in HNSCC was initially evident from a finding that caspase-triggered SREBP activation is a key molecular mechanism for HNSCC cell death under CDDP treatment [109]. A number of studies were later conducted to delineate the roles of different lipogenic proteins, including ACCs [110,111,112], FASN [113] and sphinogosine-1-phosphate metabolic enzymes [114], as well as a lipid catabolic factor lipolysis-stimulated lipoprotein receptor (LSR) [115] in controlling the HNSCC malignancy. In general, the molecules involved in lipogenesis are upregulated during HNSCC development and serve as an oncogenic indicator in clinic [110,114,116]; in contrast, lipid catabolic cues display a tumor-suppressive effect in HNSCCs.…”

Prognostic Value of the Overexpression of Fatty Acid Metabolism-Related Enzymes in Squamous Cell Carcinoma of the Head and Neck

“…Despite the endeavors in targeting aerobic glycolysis in the treatment of SCCHN, no glycolytic inhibitors have been used in the clinical setting so far [ 12 ], suggesting that SCCHN cells might have alternative metabolic pathways to acquire energy to survive. Our previous study, and a study by another group, have shown that overexpression of phosphorylated inhibitory ACC1 or ACC2 was associated with a decreased survival rate in SCCHN [ 4 , 5 ]. Since the major function of ACC1 is to regulate fatty acid metabolism, and ACC2 regulates FAO [ 13 , 14 ], the reprograming of lipid metabolism may play a role in tumor progression.…”

“…One of the hallmarks of SCCHN is the reprogramming of cellular energy metabolism [ 2 , 3 ]. SCCHN tumors expressing a high level of phosphorylated acetyl-CoA carboxylase 1 (pACC1) or ACC2 are associated with decreased survival [ 4 , 5 ]. The major cellular function of ACC is to produce malonyl-CoA from acetyl-CoA for fatty acid synthesis [ 6 ].…”

“…Despite the negative correlation of pACC1 or ACC2 expression with clinical outcome [ 4 , 5 ], it remains unclear whether the expression of the enzymes involved in FAO is associated with cancer progression in SCCHN. Therefore, this study aimed to retrospectively examine the expressions of major enzymes involved in FAO in patients with resected SCCHN and determine the correlation with clinicopathological variables.…”