scholarly journals PAX2 promotes epithelial ovarian cancer progression involving fatty acid metabolic reprogramming

2020 ◽  
Author(s):  
Yan Feng ◽  
Yong Tang ◽  
Yannan Mao ◽  
Yingzhao Liu ◽  
Desheng Yao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Metabolic Reprogramming

scholarly journals Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3388
Author(s):  
Mona Alharbi ◽  
Andrew Lai ◽  
Shayna Sharma ◽  
Priyakshi Kalita-de Croft ◽  
Nihar Godbole ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Multiple Reaction Monitoring ◽  
Metabolic Reprogramming ◽  
Ovarian Cancer Cells ◽  
Platinum Resistance ◽  
Target Cells ◽  
Glycolysis Pathway

Hypoxia is a key regulator of cancer progression and chemoresistance. Ambiguity remains about how cancer cells adapt to hypoxic microenvironments and transfer oncogenic factors to surrounding cells. In this study, we determined the effects of hypoxia on the bioactivity of sEVs in a panel of ovarian cancer (OvCar) cell lines. The data obtained demonstrate a varying degree of platinum resistance induced in OvCar cells when exposed to low oxygen tension (1% oxygen). Using quantitative mass spectrometry (Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH) and targeted multiple reaction monitoring (MRM), we identified a suite of proteins associated with glycolysis that change under hypoxic conditions in cells and sEVs. Interestingly, we identified a differential response to hypoxia in the OvCar cell lines and their secreted sEVs, highlighting the cells’ heterogeneity. Proteins are involved in metabolic reprogramming such as glycolysis, including putative hexokinase (HK), UDP-glucuronosyltransferase 1–6 (UD16), and 6-phosphogluconolactonase (6 PGL), and their presence correlates with the induction of platinum resistance. Furthermore, when normoxic cells were exposed to sEVs from hypoxic cells, platinum-resistance increased significantly (p < 0.05). Altered chemoresistance was associated with changes in glycolysis and fatty acid synthesis. Finally, sEVs isolated from a clinical cohort (n = 31) were also found to be enriched in glycolysis-pathway proteins, especially in patients with recurrent disease. These data support the hypothesis that hypoxia induces changes in sEVs composition and bioactivity that confers carboplatin resistance on target cells. Furthermore, we propose that the expression of sEV-associated glycolysis-pathway proteins is predictive of ovarian cancer recurrence and is of clinical utility in disease management.

scholarly journals Metabolic Reprogramming from Glycolysis to Fatty Acid Uptake and beta-Oxidation in Platinum-Resistant Cancer Cells

2021 ◽  
Author(s):  
Junjie Li ◽  
Yuying Tan ◽  
Guangyuan Zhao ◽  
Kai-Chih Huang ◽  
Horacio Cardenas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Single Cell ◽  
Cancer Cell ◽  
Aerobic Glycolysis ◽  
Fatty Acid Uptake ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Acid Uptake ◽  
Beta Oxidation

Increased aerobic glycolysis is widely considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during development of therapeutic resistance is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we found that cisplatin-resistant cells exhibit increased uptake of exogenous fatty acids, accompanied with decreased glucose uptake and de novo lipogenesis, indicating a reprogramming from glucose and glycolysis dependent to fatty acid uptake and beta-oxidation dependent anabolic and energy metabolism. A metabolic index incorporating measurements of glucose derived anabolism and fatty acid uptake correlates linearly to the level of resistance to cisplatin in ovarian cancer cell lines and in primary cells isolated from ovarian cancer patients. Mechanistically, the increased fatty acid uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing energy production through beta-oxidation. Consequently, blocking fatty acid beta-oxidation by a small molecule inhibitor in combination with cisplatin or carboplatin synergistically suppressed ovarian cancer proliferation in vitro and growth of patient-derived xenograft in vivo. Collectively, these findings support a new way for rapid detection of cisplatin-resistance at single cell level and a new strategy for treatment of cisplatin-resistant tumors.

scholarly journals miR‑148a‑3p suppresses epithelial ovarian cancer progression primarily by targeting c‑Met

2018 ◽  
Author(s):  
Wen Wang ◽  
Jing Dong ◽  
Maoxiu Wang ◽  
Shujuan Yao ◽  
Xiangyu Tian ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression

Abstract 4511: The role of Wnt5a signaling pathway in epithelial ovarian cancer progression

2018 ◽  
Author(s):  
Marwa Asem ◽  
Allison Young ◽  
Carlysa Oyama ◽  
Rebecca Burkhalter ◽  
Steven Buechler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cancer Progression

scholarly journals NKX2-8 deletion-induced reprogramming of fatty acid metabolism confers chemoresistance in epithelial ovarian cancer

EBioMedicine ◽  
2019 ◽  
Vol 43 ◽  
pp. 238-252 ◽  
Author(s):  
Jinrong Zhu ◽  
Geyan Wu ◽  
Libing Song ◽  
Lixue Cao ◽  
Zhanyao Tan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Epithelial Ovarian Cancer ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism

scholarly journals Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 24 ◽  
Author(s):  
Chin-Jui Wu ◽  
Vignesh Sundararajan ◽  
Bor-Ching Sheu ◽  
Ruby Yun-Ju Huang ◽  
Lin-Hung Wei
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Microenvironmental Factors ◽  
Therapeutic Opportunity ◽  
Molecular Therapeutic

Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. Despite advances in surgical and chemotherapeutic options, most patients with advanced EOC have a relapse within three years of diagnosis. Unfortunately, recurrent disease is generally not curable. Recent advances in maintenance therapy with anti-angiogenic agents or Poly ADP-ribose polymerase (PARP) inhibitors provided a substantial benefit concerning progression-free survival among certain women with advanced EOC. However, effective treatment options remain limited in most recurrent cases. Therefore, validated novel molecular therapeutic targets remain urgently needed in the management of EOC. Signal transducer and activator of transcription-3 (STAT3) and STAT5 are aberrantly activated through tyrosine phosphorylation in a wide variety of cancer types, including EOC. Extrinsic tumor microenvironmental factors in EOC, such as inflammatory cytokines, growth factors, hormones, and oxidative stress, can activate STAT3 and STAT5 through different mechanisms. Persistently activated STAT3 and, to some extent, STAT5 increase EOC tumor cell proliferation, survival, self-renewal, angiogenesis, metastasis, and chemoresistance while suppressing anti-tumor immunity. By doing so, the STAT3 and STAT5 activation in EOC controls properties of both tumor cells and their microenvironment, driving multiple distinct functions during EOC progression. Clinically, increasing evidence indicates that the activation of the STAT3/STAT5 pathway has significant correlation with reduced survival of recurrent EOC, suggesting the importance of STAT3/STAT5 as potential therapeutic targets for cancer therapy. This review summarizes the distinct role of STAT3 and STAT5 activities in the progression of EOC and discusses the emerging therapies specifically targeting STAT3 and STAT5 signaling in this disease setting.

scholarly journals Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Vivek Kumar ◽  
Sameer Gupta ◽  
Amrita Chaurasia ◽  
Manisha Sachan
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Early Stage ◽  
Ovarian Tissue ◽  
Characteristic Curve ◽  
Mirna Gene ◽  
Serum Samples ◽  
Cancer Management ◽  
Diagnostic Potential

BackgroundEpithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies among women worldwide. Early diagnosis of EOC could help in ovarian cancer management. MicroRNAs, a class of small non-coding RNA molecules, are known to be involved in post-transcriptional regulation of ~60% of human genes. Aberrantly expressed miRNAs associated with disease progression are confined in lipid or lipoprotein and secreted as extracellular miRNA in body fluid such as plasma, serum, and urine. MiRNAs are stably present in the circulation and recently have gained an importance to serve as a minimally invasive biomarker for early detection of epithelial ovarian cancer.MethodsGenome-wide methylation pattern of six EOC and two normal ovarian tissue samples revealed differential methylation regions of miRNA gene promoter through MeDIP-NGS sequencing. Based on log2FC and p-value, three hypomethylated miRNAs (miR-205, miR-200c, and miR-141) known to have a potential role in ovarian cancer progression were selected for expression analysis through qRT-PCR. The expression of selected miRNAs was analyzed in 115 tissue (85 EOC, 30 normal) and 65 matched serum (51 EOC and 14 normal) samples.ResultsAll three miRNAs (miR-205, miR-200c, and miR-141) showed significantly higher expression in both tissue and serum cohorts when compared with normal controls (p &lt; 0.0001). The receiver operating characteristic curve analysis of miR-205, miR-200c, and miR-141 has area under the curve (AUC) values of 87.6 (p &lt; 0.0001), 78.2 (p &lt; 0.0001), and 86.0 (p &lt; 0.0001), respectively; in advance-stage serum samples, however, ROC has AUC values of 88.1 (p &lt; 0.0001), 78.9 (p &lt; 0.0001), and 86.7 (p &lt; 0.0001), respectively, in early-stage serum samples. The combined diagnostic potential of the three miRNAs in advance-stage serum samples and early-stage serum samples has AUC values of 95.9 (95% CI: 0.925–1.012; sensitivity = 96.6% and specificity = 80.0%) and 98.1 (95% CI: 0.941–1.021; sensitivity = 90.5% and specificity = 100%), respectively.ConclusionOur data correlate the epigenetic deregulation of the miRNA genes with their expression. In addition, the miRNA panel (miR-205 + miR-200c + miR-141) has a much higher AUC, sensitivity, and specificity to predict EOC at an early stage in both tissue and serum samples.

scholarly journals Higher Level of Fatty Acid Synthase Enzyme Predicts Lower Rate of Completing Debulking Surgery in Epithelial Ovarian Cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 2859-2863
Author(s):  
Gatot Winarno ◽  
Yudi Hidayat ◽  
Setiawan Soetopo ◽  
Sofie Krisnadi ◽  
Maringan Tobing ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Epithelial Ovarian Cancer ◽  
Fatty Acid Synthase ◽  
Debulking Surgery

scholarly journals Bevacizumab in the Management of Epithelial Ovarian Cancer

2013 ◽  
Vol 09 (02) ◽  
pp. 129
Author(s):  
Maurie Markman ◽  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Single Agent ◽  
Strong Support ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Phase Iii ◽  
Platinum Sensitive ◽  
Platinum Resistant

Preclinical investigations have provided strong support for the hypothesis that angiogenesis is a potent driver of epithelial ovarian cancer progression. Phase II data have revealed the activity of single-agent bevacizumab in previously treated and clinically defined platinum-resistant ovarian cancer. Several reported phase III randomized trials, involving primary and both ‘platinum-sensitive’ recurrent and platinum-resistant disease, have demonstrated the addition of bevacizumab to a cytotoxic chemotherapy regimen improves progression-free survival compared with chemotherapy alone. While there continues to be considerable debate regarding the optimal dose, timing, and duration of bevacizumab administration in ovarian cancer, the existing data provide strong support for an important role for this agent in the overall management paradigm for this malignancy.

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