Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Abstract

Background/Aims: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. Methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression was achieved by RNA interference, which was confirmed by qRT-PCR and Western blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a flow cytometry analysis, respectively. Cell migration and invasion were determined by the scratch and transwell assays. Following the knockdown of ACSS2 expression, the expression of the autophagy-related factor LAMP1 was measured by qRT-PCR and Western blotting. Results: Compared to adjacent tissues, ACSS2 expression was upregulated in RCC cancer tissues and positively correlated with metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell migration and invasion. ACSS2 was determined to promote the expression of LAMP1, which can also promote cell migration. This pathway may be considered a potential mechanism through which ACSS2 participates in RCC development. Conclusion: These data suggest that ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. Taken together, these findings reveal a potential target for the diagnosis and treatment of RCC.

Metabolic rewiring in the promotion of cancer metastasis: mechanisms and therapeutic implications

“…Cytosolic and nuclear acetyl-CoA levels are maintained by four metabolic pathways: (1) direct synthesis from acetate and CoA via acetyl-CoA synthetase short-chain family (ACSS); (2) conversion from citrate to acetyl-CoA by ATP citrate lyase (ACLY); (3) its catabolism to acetate and CoA by acyl-CoA thioesterase (ACOT); and (4) irreversible carboxylation from Acetyl-CoA to malonyl-CoA by Acetyl-CoA carboxylase (ACC) [9]. Deregulation of acetyl-CoA has been reported in multiple cancers [23][24][25][26][27][28][29][30][31][32][33], and it contribute to malignant phenotypes.…”

Data Independent Acquisition Proteomic Analysis Can Discriminate between Actinic Keratosis, Bowen’s Disease, and Cutaneous Squamous Cell Carcinoma

“…Upregulation of the extracellular matrix protein BGN correlates with poor differentiation in colorectal cancers (Gu et al, 2011) and tumor invasiveness in metastatic melanoma (Andrlová et al, 2017). Overexpression of AACS is linked with increased invasiveness in colorectal (Ding et al, 2017) and renal cell carcinomas (Yao et al, 2018), and increased HP1BP3 is linked with chemoresistant colorectal cancer (Hadac et al, 2016). The ability to accurately discriminate stages of cSCC differentiation has significant implications for clinical management.…”

Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools

“…Dynamic pH can also directly regulate transcription factors to drive phenotypic plasticity in cancer. For example, acidic culture conditions can induce nuclear localization of the Sterol Regulatory Element-binding protein 2 (SREB2), driving the transcription of twelve pH-responsive genes including acetyl-CoA synthetase 2 (ACSS2), 3-hydroxy-3-methylglutaryl-CoA synthase 1(HMGCS1), farnesyl diphosphate farnesyltransferase (FDFT1), and low density lipoprotein receptor (LDLR) [ 53 ] that contribute to invasion [ 54 ] (ACSS2), proliferation [ 55 ] (FDFT1), increased growth rates [ 56 ] (HMGCS1), and advanced tumor grades [ 57 ] (LDLR). Further, all nine cancers analyzed by Kondo et al displayed lower overall survival in patients with high expression of the twelve pH-responsive genes, reinforcing the role that pH may play in cancer establishment and progression through metabolic alterations in response to environment [ 53 ].…”