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Epithelial ovarian cancer (EOC), a leading cause of gynecological cancer-related morbidity and mortality and the most common type of ovarian cancer (OC), is widely characterized by alterations in the Epidermal Growth Factor (EGF) signaling pathways. The phenomenon of metastasis is largely held accountable for the majority of EOC-associated deaths. Existing literature reports substantiate evidence on the indispensable role of metabolic reprogramming, particularly the phenomenon of the 'Warburg effect' or aerobic glycolysis in priming the cancer cells towards Epithelial to Mesenchymal transition (EMT), subsequently facilitating EMT. Considering the diverse roles of growth factor signaling across different stages of oncogenesis, our prime emphasis was laid on unraveling mechanistic details of EGF-induced 'Warburg effect' and resultant metastasis in EOC cells. Our study puts forth Ets1, an established oncoprotein and key player in OC progression, as the prime metabolic sensor to EGF-induced cues from the tumor microenvironment (TME). EGF treatment has been found to induce Ets1 expression in OC cells predominantly through the Extracellular Signal-Regulated Kinase1/2 (ERK1/2) pathway activation. This subsequently results in pronounced glycolysis, characterized by an enhanced lactate production through transcriptional up-regulation of key determinant genes of the central carbon metabolism namely, hexokinase 2 (HK2) and monocarboxylate transporter 4 (MCT4). Furthermore, this study reports an unforeseen combinatorial blockage of HK2 and MCT4 as an effective approach to mitigate cellular metastasis in OC. Collectively, our work proposes a novel mechanistic insight into EGF-induced glycolytic bias in OC cells and also sheds light on an effective therapeutic intervention approach exploiting these insights.
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http://dx.doi.org/10.1016/j.bbamcr.2024.119805 | DOI Listing |
J Cell Mol Med
December 2024
Biosciences Institute, Newcastle University Cancer Centre, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Polycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA.
View Article and Find Full Text PDFThe advent of poly(ADP-ribose) polymerase (PARP) inhibitors has resulted in a significant paradigm shift in ovarian cancer treatment. Niraparib, a potent PARP inhibitor, has demonstrated substantial efficacy in both first-line and recurrent disease settings. By targeting homologous recombination DNA repair, a pathway frequently disrupted in ovarian cancer, particularly in the context of BRCA mutations, niraparib induces synthetic lethality.
View Article and Find Full Text PDFExp Ther Med
February 2025
Department of Orthopedics, Tianjin Hospital, Tianjin 300211, P.R. China.
The aim of the present study was to explore the role of ovarian cancer G protein-coupled receptor 1 (OGR1) in osteoclast differentiation and activity induced by extracellular acid. The impact of extracellular acidification on osteoclasts was investigated. Briefly, osteoclasts were generated from RAW 264.
View Article and Find Full Text PDFWorld J Clin Oncol
December 2024
Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon.
Background: The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.
Aim: To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.
Methods: We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.
EClinicalMedicine
January 2025
Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynaecological Diseases, State Key Laboratory of Common Mechanism Research for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: Ovarian cancer (OC) is a heterogeneous malignancy with multiple histological subtypes, showing global variability in incidence. Temporal changes in diagnostic criteria and risk factors might influence the incidence and distribution of OC and its subtypes.
Methods: This study analyzed incidence patterns (2013-2017) and trends (1988-1992 to 2013-2017) of OC and its subtypes across 65 and 40 countries, respectively.
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