Obesity and Energy Substrate Transporters in Ovarian Cancer—Review

Baczewska, Marta; Bojczuk, Klaudia; Kołakowski, Adrian; Dobroch, Jakub; Guzik, Paweł; Knapp, Paweł

doi:10.3390/molecules26061659

Cited by 13 publications

(8 citation statements)

References 110 publications

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“…Cancer cells also upregulate fatty acid synthase, which converts acetyl-CoA to long-chain fatty acids [153]. In addition, extracellular fatty acids are taken avidly by cancer cells via multiple transport mechanisms [154]. Taken collectively, it has become clear in recent years that selective nutrient transporters are obligatory to drive the reprogrammed cancer cell metabolism.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Signature of Warburg Effect in Cancer: An Effective and Obligatory Interplay between Nutrient Transporters and Catabolic/Anabolic Pathways to Promote Tumor Growth

Mathew,

Nguyen,

Bhutia

et al. 2024

Cancers

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Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves the production of lactate as the end product of glucose breakdown even in the presence of adequate oxygen, is the foundation for the current interest in the cancer-cell-specific reprograming of metabolic pathways. The renewed interest in cancer cell metabolism has now gone well beyond the original Warburg effect related to glycolysis to other metabolic pathways that include amino acid metabolism, one-carbon metabolism, the pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since glucose and amino acids constitute the primary nutrients that fuel the altered metabolic pathways in cancer cells, the transporters that mediate the transfer of these nutrients and their metabolites not only across the plasma membrane but also across the mitochondrial and lysosomal membranes have become an integral component of the expansion of the Warburg effect. In this review, we focus on the interplay between these transporters and metabolic pathways that facilitates metabolic reprogramming, which has become a hallmark of cancer cells. The beneficial outcome of this recent understanding of the unique metabolic signature surrounding the Warburg effect is the identification of novel drug targets for the development of a new generation of therapeutics to treat cancer.

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Section: Discussionmentioning

confidence: 99%

Metabolic Signature of Warburg Effect in Cancer: An Effective and Obligatory Interplay between Nutrient Transporters and Catabolic/Anabolic Pathways to Promote Tumor Growth

Mathew,

Nguyen,

Bhutia

et al. 2024

Cancers

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“…OC cells not only express high levels of FASN, the rate-limiting enzyme in FA synthesis [ 12 , 13 , 44 ], and show hyperactive endogenous lipogenesis [ 15 , 16 , 17 , 18 ], but they also contain numerous lipid receptors and transport proteins, such as FAT/CD36, LDLR, FABPs, and FATP2/SLC27A2, enabling the cells to vigorously import lipids from extracellular compartments such as ascites [ 14 , 46 , 47 , 48 , 49 ]. Membrane-bound FA channel protein FAT/CD36 and receptor protein LDLR are major entrance ports for lipids.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Lipid Import and Transport Proteins in Ovarian Cancer

Lemberger

Wagner

Heller

et al. 2022

Cancers

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Ovarian cancer (OC) is the most lethal gynecological malignancy with a 5-year survival rate of 49%. This is caused by late diagnosis when cells have already metastasized into the peritoneal cavity and to the omentum. OC progression is dependent on the availability of high-energy lipids/fatty acids (FA) provided by endogenous de novo biosynthesis and/or through import from the microenvironment. The blockade of these processes may thus represent powerful strategies against OC. While this has already been shown for inhibition of FA/lipid biosynthesis, evidence of the role of FA/lipid import/transport is still sparse. Therefore, we treated A2780 and SKOV3 OC cells with inhibitors of the lipid uptake proteins fatty acid translocase/cluster of differentiation 36 (FAT/CD36) and low-density lipoprotein (LDL) receptor (LDLR), as well as intracellular lipid transporters of the fatty acid-binding protein (FABP) family, fatty acid transport protein-2 (FATP2/SLC27A2), and ADP-ribosylation factor 6 (ARF6), which are overexpressed in OC. Proliferation was determined by formazan dye labeling/photometry and cell counting. Cell cycle analysis was performed by propidium iodide (PI) staining, and apoptosis was examined by annexin V/PI and active caspase 3 labeling and flow cytometry. RNA-seq data revealed altered stress and metabolism pathways. Overall, the small molecule inhibitors of lipid handling proteins BMS309403, HTS01037, NAV2729, SB-FI-26, and sulfosuccinimidyl oleate (SSO) caused a drug-specific, dose-/time-dependent inhibition of FA/LDL uptake, associated with reduced proliferation, cell cycle arrest, and apoptosis. Our findings indicate that OC cells are very sensitive to lipid deficiency. This dependency should be exploited for development of novel strategies against OC.

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“…Increased expression of GLUT1 is associated with shorter survival times in ovarian cancer patients and predicts a shorter time for recurrence (DFI) in patients who achieve remission. [16][17][18][19][20]…”

Section: Discussionmentioning

confidence: 99%

High Random Blood Glucose Level before Surgery as a Risk Factor for Recurrent Event in Epithelial Ovarian Carcinoma

Hapsari

Iskandar

2022

Indones J Obstet Gynecol

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Abstract Objective : To investigate the high random blood glucose level as a risk factor for recurrent disease in EOC patient at Kariadi General Hospital. Methods: Sixty six patients diagnosed as EOC in Kariadi General Hospital were divided into 2 groups: 30 patients with recurrent disease and 30 patients without recurrent disease after completing chemotherapy cycles. We analysed correlation between age of diagnosis, tumour mass location, Ca-125 level, histological subtype and random blood glucose level before surgery with recurrent disease. Result: There is no significantly difference in age of diagnosis, tumour mass location and histological subtypes between two groups. However, recurrent EOC patients have higher Ca-125 level significantly than non-recurrent patients (327.8±250.5 vs 183.5±212.1 respectively; p = 0,01). Mean of random blood glucose level of recurrent patients is also higher than non-recurrent patients significantly (150.5 ±79 vs 110.8 ± 31.1 respectively; p = 0.006). Patient with random blood glucose level > 110 mg/dl have 3 times more likely to develop recurrence in EOC patient significantly with 95% CI. Conclusion: The mean of random blood glucose level in recurrent EOC patients is significantly higher than non-recurrent EOC patients. Patient with random blood glucose level > 110 mg/dl have 3 times more likely to develop recurrence in EOC patient. Keyword: epithelial ovarian cancer, random blood glucose level, recurrent. Abstrak Tujuan: Untuk membuktikan kadar glukosa darah sewaktu yang tinggi sebagai faktor risiko kejadian residif pada pasien karsinoma ovarium epitelial di RSUP dr. Kariadi. Metode: Enam puluh pasien yang telah didiagnosis sebagai karsinoma ovarium epitelial di RSUP dr. Kariadi dibagi menjadi 2 kelompok: 30 pasien pada kelompok residif dan 30 pasien pada kelompok non-residif berdasarkan evaluasi setelah menyelesaikan siklus kemoterapi. Data yang dianalisis meliputi usia saat terdiagnosis, lokasi tumor, kadar Ca-125, subtipe histologi, kadar gula darah sewaktu (GDS) sebelum operasi dan hubungannya dengan kejadian residif. Hasil: Tidak terdapat perbedaan yang bermakna dalam usia saat diagnosis, lokasi tumor dan subtipe histologis diantara kedua kelompok. Namun, kelompok pasien residif memiliki kadar Ca-125 yang lebih tinggi secara bermakna dibandingkan kelompok pasien non-residif (327,8 ± 250,5 vs 183,5 ± 212,1; p = 0,01). Rerata kadar GDS pada kelompok pasien residif juga lebih tinggi secara bermakna daripada kelompok non-residif (150,5 ± 79 vs 110,8 ± 31,1; p = 0,006). Pasien dengan kadar GDS > 110 mg/dl memiliki risiko 3 kali lipat untuk menjadi residif secara bermakna dengan tingkat kepercayaan 95%. Kesimpulan: Rerata kadar GDS pada kelompok pasien residif lebih tinggi secara bermakna dibanding kelompok pasien non-residif. Pasien dengan kadar GDS > 110 mg/dl memiliki risiko 3 kali lipat untuk menjadi residif Kata kunci: kadar gula darah sewaktu, karsinoma ovarium epitelial, residif.

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Obesity and Energy Substrate Transporters in Ovarian Cancer—Review

Cited by 13 publications

References 110 publications

Metabolic Signature of Warburg Effect in Cancer: An Effective and Obligatory Interplay between Nutrient Transporters and Catabolic/Anabolic Pathways to Promote Tumor Growth

Metabolic Signature of Warburg Effect in Cancer: An Effective and Obligatory Interplay between Nutrient Transporters and Catabolic/Anabolic Pathways to Promote Tumor Growth

Pharmacological Inhibition of Lipid Import and Transport Proteins in Ovarian Cancer

High Random Blood Glucose Level before Surgery as a Risk Factor for Recurrent Event in Epithelial Ovarian Carcinoma

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