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Ovarian cancer(OC) is a serious threat to women worldwide. Peritoneal dissemination, ascites and omental metastasis are typical features for disease progression, which occurs in a micro-environment that is rich in high-energy lipids. OC cells require high amounts of lipids for survival and growth. Not only do they import lipids from the host, they also produce lipids . Inhibitors of fatty acid(FA) synthase(FASN) - the rate-limiting enzyme of endogenous FA synthesis that is overexpressed in OC - induce growth-arrest and apoptosis, rendering them promising candidates for cancer drug development. However, cancer researchers have long hypothesized that the lipid deficiency caused by FASN inhibition can be circumvented by increasing the uptake of exogenous lipids from the host, which would confer resistance to FASN inhibitors. In contrast to a very recent report in colorectal cancer, we demonstrate in OC cells (A2780, OVCAR3, SKOV3) that neither FASN inhibitors (G28UCM, Fasnall) nor FASN-specific siRNAs can stimulate a relief pathway leading to enhanced uptake of extrinsic FAs or low density lipoproteins (LDLs). Instead, we observed that the growth-arrest due to FASN inhibition or FASN knock-down was associated with significant dose- and time-dependent reduction in the uptake of fluorescently labeled FAs and LDLs. Western blotting showed that the expression of the FA receptor CD36, the LDL receptor(LDLR) and the lipid transport proteins fatty acid binding proteins 1-9 (FABP1-9) was not affected by the treatment. Next, we compared experimental blockade of endogenous lipid production with physiologic depletion of exogenous lipids. Lipid-free media, similar to FASN inhibitors, caused growth-arrest. Although lipid-depleted cells have diminished amounts of CD36, LDLR and FABPs, they can still activate a restorative pathway that causes enhanced import of fluorophore-labeled FAs and LDLs. Overall, our data show that OC cells are strictly lipid-depend and exquisitely sensitive to FASN inhibitors, providing a strong rationale for developing anti-FASN strategies for clinical use against OC.
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http://dx.doi.org/10.3389/fonc.2021.610885 | DOI Listing |
Cell Death Dis
December 2024
Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Bladder cancer (BC) is the second most prevalent genitourinary malignancy worldwide. Despite recent approvals of immune checkpoint inhibitors and targeted therapy for muscle invasive or recurrent BC, options remain limited for patients with non-muscle invasive BC (NMIBC) refractory to Bacillus Calmette-Guérin (BCG) and chemotherapy. NMIBC is more frequently classified as a luminal subtype, in which increased PPARγ activity is a key feature in promoting tumor growth and evasion of immunosurveillance.
View Article and Find Full Text PDFAust J Gen Pract
December 2024
FRCP, FRACP, Consultant Physician, Department of General Medicine and Acute Assessment Unit, Canberra Hospital, Canberra, ACT; Clinical Associate Professor, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA; Associate Professor, ANU College of Health and Medicine, Australian National University, Canberra, ACT.
Background: Chronic kidney disease (CKD) is a significant healthcare problem. More advanced stages are associated with increased mortality, morbidity and cost. Instigating measures to slow down disease progression at an early stage can save lives, and millions of dollars of taxpayers' money.
View Article and Find Full Text PDFAnimals (Basel)
November 2024
College of Animal Science and Technology, Hebei Agricultural University, Baoding 071001, China.
Prolactin (PRL) has recently been found to play a role in lipid metabolism in addition to its traditional roles in lactation and reproduction. However, the effects of PRL on lipid metabolism in liver and adipose tissues are unclear. Therefore, we aimed to study the role of PRL on lipid metabolism in goats.
View Article and Find Full Text PDFHeliyon
December 2024
Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215153, China.
Circadian disruption is a risk factor for Parkinson's disease (PD). Ferroptosis, a cellular death process, assumes a pivotal role in the degeneration of dopaminergic neurons in PD. Despite its significance, the potential contribution of circadian clock proteins to PD through the modulation of ferroptosis remains elusive.
View Article and Find Full Text PDFAntiviral Res
December 2024
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, China; Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing, 163319, China; Engineering Research Center for Prevention and Control of Cattle Diseases, Heilongjiang Province, Daqing, 163319, China. Electronic address:
For many viruses, controlling the process of infection is largely dependent on the enzymes of the fatty acid synthesis (FAS) pathway. An appealing therapeutic target in antiviral research is fatty acid synthetase (FASN), a crucial enzyme in the FAS pathway. Bovine viral diarrhea, caused by the Bovine viral diarrhea virus (BVDV), is a significant viral infectious disease posing a substantial threat to global animal husbandry.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!