卵巢透明细胞癌（OCCC）具有独特的临床特征，起源于良性子宫内膜异位囊肿，由于铁积累过多而形成氧化应激环境，并且由于对常规治疗产生耐药性而表现出不良预后，特别是在晚期。铁死亡是一种铁依赖性程序性细胞死亡形式，由脂质过氧化诱导并由 Hippo 信号传导控制。我们假设克服铁死亡抗性是一种有吸引力的策略，因为 OCCC 在其发育过程中获得了氧化应激抗性，并表现出表明铁死亡抗性的化学抗性特征。本研究旨在确定 OCCC 是否对铁死亡具有抵抗力并阐明抵抗力的机制。与卵巢高级别浆液性癌细胞不同，OCCC 细胞暴露于氧化应激。然而，OCCC 细胞仍未受到脂质过氧化的影响。细胞活力测定显示 OCCC 细胞表现出对铁死亡诱导剂erastin 的抗性。此外，Samroc 分析表明 Hippo 信号通路在 OCCC 细胞系和临床样本中富集。此外，核Yes相关蛋白1（YAP1）低表达的患者表现出明显较差的OCCC预后。此外，YAP1 激活增强了 OCCC 细胞系中的铁死亡。此外，抑制锌指 DHHC 型棕榈酰转移酶 7 (ZDHHC7) 可通过激活 OCCC 细胞系中的 YAP1 来增强铁死亡。小鼠异种移植模型表明，ZDHHC7 抑制通过erastin 治疗激活 YAP1 来抑制肿瘤生长。总之，ZDHHC7 调节的 YAP1 激活增强了 OCCC 中的铁死亡。因此，克服铁死亡抵抗是 OCCC 的潜在治疗策略。

Ovarian clear cell carcinoma (OCCC), which has unique clinical characteristics, arises from benign endometriotic cysts, forming an oxidative stress environment due to excess iron accumulation, and exhibits poor prognosis, particularly in advanced stages owing to resistance to conventional therapeutics. Ferroptosis is an iron-dependent form of programmed cell death induced by lipid peroxidation and controlled by Hippo signaling. We hypothesized that overcoming ferroptosis resistance is an attractive strategy because OCCC acquires oxidative stress resistance during its development and exhibits chemoresistant features indicative of ferroptosis resistance. This study aimed to determine whether OCCC is resistant to ferroptosis and clarify the mechanism underlying resistance. Unlike ovarian high-grade serous carcinoma cells, OCCC cells were exposed to oxidative stress. However, OCCC cells remained unaffected by lipid peroxidation. Cell viability assays revealed that OCCC cells exhibited resistance to the ferroptosis inducer erastin. Moreover, Samroc analysis showed that the Hippo signaling pathway was enriched in OCCC cell lines and clinical samples. Furthermore, patients with low expression of nuclear Yes-associated protein 1(YAP1) exhibited a significantly poor prognosis of OCCC. Moreover, YAP1 activation enhanced ferroptosis in OCCC cell lines. Furthermore, suppression of zinc finger DHHC-type palmitoyltransferase 7 (ZDHHC7) enhanced ferroptosis by activating YAP1 in OCCC cell lines. Mouse xenograft models demonstrated that ZDHHC7 inhibition suppressed tumor growth via YAP1 activation by erastin treatment. In conclusion, YAP1 activation regulated by ZDHHC7 enhanced ferroptosis in OCCC. Thus, overcoming ferroptosis resistance is a potential therapeutic strategy for OCCC.