Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27708, USA.
Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710006, China.
Cell Rep. 2022 Jun 28;39(13):111012. doi: 10.1016/j.celrep.2022.111012.
Ovarian cancer (OC) is the most lethal gynecological malignancy, with aggressive metastatic disease responsible for the majority of OC-related deaths. In particular, OC tumors preferentially metastasize to and proliferate rapidly in the omentum. Here, we show that metastatic OC cells experience increased oxidative stress in the omental microenvironment. Metabolic reprogramming, including upregulation of the pentose phosphate pathway (PPP), a key cellular redox homeostasis mechanism, allows OC cells to compensate for this challenge. Inhibition of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, reduces tumor burden in pre-clinical models of OC, suggesting that this adaptive metabolic dependency is important for OC omental metastasis.
卵巢癌（OC）是最致命的妇科恶性肿瘤，其侵袭性转移性疾病是导致大多数 OC 相关死亡的主要原因。特别是，OC 肿瘤优先转移并在大网膜中快速增殖。在这里，我们表明转移性 OC 细胞在大网膜微环境中经历增加的氧化应激。代谢重编程，包括戊糖磷酸途径（PPP）的上调，这是一种关键的细胞氧化还原稳态机制，使 OC 细胞能够补偿这一挑战。葡萄糖-6-磷酸脱氢酶（G6PD）的抑制，PPP 的限速酶，减少 OC 的临床前模型中的肿瘤负担，表明这种适应性代谢依赖性对于 OC 大网膜转移很重要。
