scholarly journals Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells

Oncotarget ◽  
2017 ◽  
Vol 8 (7) ◽  
pp. 11600-11613 ◽  
Author(s):  
Renate Wagner ◽  
Gerald Stübiger ◽  
Daniel Veigel ◽  
Michael Wuczkowski ◽  
Peter Lanzerstorfer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Ovarian Cancer Cells ◽  
Multi Level

scholarly journals Fatty Acid Synthase Inhibition Activates AMP-Activated Protein Kinase in SKOV3 Human Ovarian Cancer Cells

2007 ◽  
Vol 67 (7) ◽  
pp. 2964-2971 ◽  
Author(s):  
Weibo Zhou ◽  
Wan Fang Han ◽  
Leslie E. Landree ◽  
Jagan N. Thupari ◽  
Michael L. Pinn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Amp Activated Protein Kinase

Interaction between fatty acid synthase- and ErbB-systems in ovarian cancer cells

2009 ◽  
Vol 385 (3) ◽  
pp. 454-459 ◽  
Author(s):  
Thomas W. Grunt ◽  
Renate Wagner ◽  
Michael Grusch ◽  
Walter Berger ◽  
Christian F. Singer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Ovarian Cancer Cells

scholarly journals Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Stefanie M. Ueda ◽  
Kai Lee Yap ◽  
Ben Davidson ◽  
Yuan Tian ◽  
Vivek Murthy ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Dominant Negative ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Primary Tumors ◽  
Ovarian Serous Carcinoma ◽  
Skov3 Cells

Our previous reports demonstrated that NAC1, a BTB/POZ domain-containing nuclear protein, upregulates in recurrent ovarian serous carcinoma and participates in developing drug resistance in cancer cells. The current study applies quantitative proteomics to identify the proteins controlled by NAC1 by comparing the proteomes of SKOV3 cells with and without expression of a dominant negative NAC1 construct, N130. From the proteins that are downregulated by N130 (upregulated by NAC1), we chose to further characterize fatty acid synthase (FASN). Similar to change in protein level, the FASN transcript level in SKOV3 cells was significantly reduced by N130 induction or by NAC1 knockdown. Immunohistochemistry showed that NAC1 and FASN immunointensities in ovarian serous carcinoma tissues had a highly significant correlation (P<.0001). Moreover, we found that recurrent serous carcinomas exhibited higher FASN immunointensities than their matched primary tumors (P<.001). Multivariate analysis showed that an FASN staining score of >1 in serous carcinomas was associated with a worse overall survival time (P<.01). Finally, C93, a new FASN inhibitor, induced massive apoptosis in carboplatin/paclitaxel resistant ovarian cancer cells. In conclusion, we show that NAC1 is essential for FASN expression in ovarian serous carcinomas and the expression of FASN significantly correlates with tumor recurrence and disease aggressiveness. The dependence of drug resistant tumor cells on FASN suggests a potential application of FASN-based therapeutics for recurrent ovarian cancer patients.

scholarly journals Acyl-CoA Medium-Chain Synthetase-3 Promotes Chemosensitivity of Ovarian Cancer through the Inhibition of PI3K/AKT Signaling Pathway

2021 ◽  
Author(s):  
Yuanyuan An ◽  
Hua Duan
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Immune Status ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Akt Signaling Pathway

Abstract Introduction: Dysregulation of fatty acid metabolism often occurs in tumor, which mainly constitutes of fatty acid synthesis and oxidation. In recent years, studies found that fatty acid metabolism participated in regulation of tumor immune microenvironment, which further influenced the progress of cancer. Thus, it is important to explore the key fatty acid metabolism-related molecules, which not only affects the prognosis of ovarian cancer, but also shows a close correlation with immune microenvironment of cancer.Methods: Database from TCGA was used to explore the fatty acid metabolism-related molecules, which correlated with the prognosis of ovarian cancer using univariate and multivariate cox proportional regression model. Nomogram was constructed to predict the prognostic probability based on ACSM3 and clinicopathological parameters. GDSC database was used to investigate the chemosensitivity of ovarian cancer cells. The correlation between ACSM3 and immune status of ovarian cancer was analyzed by TIMER and TISIDB online tools. In addition, CCK8 assay was used to investigate the chemosensitivity of ovarian cancer cells, real time-PCR and western blot were used to investigate the expression of chemoresistance-related genes.Results: ACSM3 worked as an independent favorable prognostic molecule through univariate and multivariate cox regression analysis. For the use in clinical, nomogram was constructed, and higher expression of ACSM3 showed better prognosis. We found that ACSM3 could regulate PI3K/AKT signaling, and GDSC database showed that PI3K/AKT inhibitor could promote the chemosensitivity of ovarian cancer cells. In addition, the expression of ACSM3 showed significantly correlated with the immune status of ovarian cancer. In vitro experiments showed that ACSM3 can promote the chemosensitivity of ovarian cancer cells by inhibiting PI3K/AKT signaling pathway.Conclusion: Our results showed that ACSM3 acted as a favorable prognostic-related biomarker for ovarian cancer, which could promote chemosensitivity of ovarian cancer through inhibiting PI3K/AKT signaling pathway. This might be due to participate in regulating immune status of ovarian cancer microenvironment.

scholarly journals Ovarian Cancer—Why Lipids Matter

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1870 ◽  
Author(s):  
Guangyuan Zhao ◽  
Horacio Cardenas ◽  
Daniela Matei
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Fatty Acid Desaturase ◽  
Response To Therapy ◽  
Ovarian Cancer Cells ◽  
Lipid Uptake ◽  
Oncogenic Signaling ◽  
Ovarian Cancer Stem Cells

This review highlights recent advances in the understanding of the relevance of altered lipid metabolic pathways contributing to the poor prognosis of high grade serous ovarian cancer, as they relate to cancer metastasis and cancer stemness. Increased lipid uptake regulated by the receptor CD36 and the transport protein FABP4 has been implicated in ovarian cancer metastasis. The symbiotic relationship between ovarian cancer cells and adipocytes was shown to be important for sustaining widespread peritoneal and omental metastasis. Increased lipogenesis dependent on the fatty acid desaturase SCD1 was detected in ovarian cancer stem cells. Furthermore, response to therapy, specifically to platinum, was linked to increased fatty acid biogenesis, while the survival of drug tolerant cells was shown to depend on lipid peroxidation. These recent findings suggest that lipids are necessary elements supporting oncogenic signaling and the energetic needs of rapidly proliferating cancer cells. New strategies targeting key enzymes involved in lipid uptake or utilization in cancer cells have been shown to exert anti-tumor effects and are being developed as cancer interventions in combination with chemotherapy or immunotherapy.

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