Abstract
HNF1β is expressed exclusively in ovarian clear cell carcinoma (OCCC) and not in other ovarian cancers, regarded as a hallmark of this tumor. This implies its central role in the unique character of OCCC, including resistance to chemotherapy, but its exact role and influence in cancer biology or the molecular bases of its function are largely unknown. Using comprehensive metabolome analysis of HNF1β_shRNA-stable cell lines, we show here that HNF1β drastically alters intracellular metabolism, especially in direction to enhance aerobic glycolysis, so called the "Warburg effect". The consequence of the metabolic change contributed cell survival under stresses such as hypoxia and chemo-reagent, only when sufficient glucose supply was available. Augmented cell survival was based on the reduced ROS activity derived from metabolic alteration such as shift from oxidative phosphorylation to glycolysis and increased intracellular anti-oxidant, glutathione (GSH). One of the cystine transporters, rBAT is likely to play a major role in this GSH increase. These data suggest that HNF1β, possibly induced by stressful microenvironment in the endometriotic cyst, confers survival advantage to the epithelial cells, which leads to the occurrence of OCCC, a chemo-resistant phenotype of ovarian cancer.
Highlights
Ovarian clear cell carcinoma (OCCC) is a relatively rare subtype among the ovarian cancers, but is a clinically important entity because it is generally resistant to chemotherapy and is known to have a worse prognosis compared with other ovarian cancers [1,2,3,4]
The samples in each dataset were divided into the OCCC group and the non-OCCC group, and gene sets enriched in the OCCC group were extracted and analyzed
We have previously shown that hepatocyte nuclear factor 1β (HNF1β), a molecule that is expressed in high frequency and specificity in OCCC, facilitates glucose uptake and promotes concomitant glycolysis, leading to increased lactic acid production [25]
Summary
Ovarian clear cell carcinoma (OCCC) is a relatively rare subtype among the ovarian cancers, but is a clinically important entity because it is generally resistant to chemotherapy and is known to have a worse prognosis compared with other ovarian cancers [1,2,3,4]. Another clinical feature of OCCC is its frequent occurrence in endometriotic cysts, so called “chocolate cysts”. The choice between cell survival and death depends on the balance between ROS production and potential for elimination
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
