Association of Lipid Metabolism with Ovarian Cancer

Tania, M.; Khan, Md. Asaduzzaman; Song, Yuanda

doi:10.3747/co.v17i5.668

Cited by 76 publications

(33 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, the metabolic proteins transketolase and enolase, which are involved in glycolysis and the pentose phosphate pathway, respectively, were found to be differentially expressed by septin-2 inhibition (Figure 4C), demonstrating that septin-2 is involved in various facets of cellular metabolism within EOC. Pathways related to metabolism and energy production have previously been found to contribute to EOC tumorigenesis, as it has been shown that glycolysis drives chemoresistance in EOC and that high levels of fatty acid synthase (FASN) contribute to tumor cell growth through the promotion of human epidermal growth factor [44, 45]. Therefore, it can be hypothesized that the inhibition of septin-2 would exhibit a therapeutic effect in EOC via suppression of tumor metabolic pathways.…”

Section: Discussionmentioning

confidence: 99%

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

et al. 2019

View full text Add to dashboard Cite

Epithelial Ovarian Cancer (EOC) is associated with dismal survival rates due to the fact that patients are frequently diagnosed at an advanced stage and eventually become resistant to traditional chemotherapeutics. Hence, there is a crucial need for new and innovative therapies. Septin-2, a member of the septin family of GTP binding proteins, has been characterized in EOC for the first time and represents a potential future target. Septin-2 was found to be overexpressed in serous and clear cell human patient tissue compared to benign disease. Stable septin-2 knockdown clones developed in an ovarian cancer cell line exhibited a significant decrease in proliferation rates. Comparative label-free proteomic analysis of septin-2 knockdown cells revealed differential protein expression of pathways associated with the TCA cycle, acetyl CoA, proteasome and spliceosome. Further validation of target proteins indicated that septin-2 plays a predominant role in post-transcriptional and translational modifications as well as cellular metabolism, and suggested the potential novel role of septin-2 in promoting EOC tumorigenesis through these mechanisms.

show abstract

Section: Discussionmentioning

confidence: 99%

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In a meta-analysis, 24 of 28 studies reported a positive association between obesity and ovarian cancer ( 9 ). Overexpression of some lipid metabolic enzymes is also found in ovarian cancer ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Serum CA125 Concentration has Inverse Correlation with Metabolic Syndrome

Joo

Kim

2011

J Korean Med Sci

View full text Add to dashboard Cite

Serum carbohydrate antigen 125 (CA-125) is a marker of ovarian cancer and obesity that is related with an increased risk of ovarian cancer. Obesity is a key factor of metabolic syndrome. We evaluated the relationship between CA-125 concentration and metabolic syndrome. The data from subjects who had any cancer and chronic infection were excluded. The data of 12,196 healthy Korean women were analyzed. After CA-125 concentration was divided by quartiles, the prevalence of metabolic syndrome and its components were compared. The lowest quartile of CA-125 compared with the highest quartile showed elevated values of most of metabolic parameters. In addition, as the quartile of CA-125 increased, metabolic derangement decreased. Increased numbers of metabolic syndrome components showed an inverse association with CA-125 levels (P < 0.001). The odds ratio (OR) for the lowest CA-125 quartile vs the highest CA-125 quartile significantly increased in the presence of metabolic syndrome (OR = 1.202, 95% Confidence Interval [CI] 1.013-1.423), elevated triglyceride (OR = 1.381, 95% CI 1.167-1.633), and low high-density lipoprotein cholesterol (OR = 1.168, 95% CI 1.039-1.312). The presence of metabolic syndrome, elevated triglyceride, or low high-density lipoprotein cholesterol negatively correlates with CA-125 concentration.

show abstract

“…Aberrant cellular metabolism in cancer is now well known and is directly related to tumorigenesis in most of the cancers [ 57 , 58 ]. Multiple signaling pathways and several molecules are involved in the synthesis and degradation of the lipids and also the activities of lipid metabolizing enzymes are regulated by a complex interplay between metabolic, tumor suppressor, and oncogenic signaling [ 59 ]. Though loss of HSulf-1, a putative tumor suppressor gene, was well known to promote tumorigenesis, angiogenesis [ 22 , 23 ], and invasion [ 20 ] in breast [ 18 , 21 ] and ovarian [ 23 , 24 ] cancers, the role of HSulf-1 was never elucidated in altered metabolism of ovarian cancer cells so far.…”

Section: Discussionmentioning

confidence: 99%

Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer

et al. 2014

View full text Add to dashboard Cite

BackgroundLoss of the endosulfatase HSulf-1 is common in ovarian cancer, upregulates heparin binding growth factor signaling and potentiates tumorigenesis and angiogenesis. However, metabolic differences between isogenic cells with and without HSulf-1 have not been characterized upon HSulf-1 suppression in vitro. Since growth factor signaling is closely tied to metabolic alterations, we determined the extent to which HSulf-1 loss affects cancer cell metabolism.ResultsIngenuity pathway analysis of gene expression in HSulf-1 shRNA-silenced cells (Sh1 and Sh2 cells) compared to non-targeted control shRNA cells (NTC cells) and subsequent Kyoto Encyclopedia of Genes and Genomics (KEGG) database analysis showed altered metabolic pathways with changes in the lipid metabolism as one of the major pathways altered inSh1 and 2 cells. Untargeted global metabolomic profiling in these isogenic cell lines identified approximately 338 metabolites using GC/MS and LC/MS/MS platforms. Knockdown of HSulf-1 in OV202 cells induced significant changes in 156 metabolites associated with several metabolic pathways including amino acid, lipids, and nucleotides. Loss of HSulf-1 promoted overall fatty acid synthesis leading to enhance the metabolite levels of long chain, branched, and essential fatty acids along with sphingolipids. Furthermore, HSulf-1 loss induced the expression of lipogenic genes including FASN, SREBF1, PPARγ, and PLA2G3 stimulated lipid droplet accumulation. Conversely, re-expression of HSulf-1 in Sh1 cells reduced the lipid droplet formation. Additionally, HSulf-1 also enhanced CPT1A and fatty acid oxidation and augmented the protein expression of key lipolytic enzymes such as MAGL, DAGLA, HSL, and ASCL1. Overall, these findings suggest that loss of HSulf-1 by concomitantly enhancing fatty acid synthesis and oxidation confers a lipogenic phenotype leading to the metabolic alterations associated with the progression of ovarian cancer.ConclusionsTaken together, these findings demonstrate that loss of HSulf-1 potentially contributes to the metabolic alterations associated with the progression of ovarian pathogenesis, specifically impacting the lipogenic phenotype of ovarian cancer cells that can be therapeutically targeted.

show abstract

Association of Lipid Metabolism with Ovarian Cancer

Cited by 76 publications

References 53 publications

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

Serum CA125 Concentration has Inverse Correlation with Metabolic Syndrome

Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer

Contact Info

Product

Resources

About