Department of Biochemistry & Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Center for Singl-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Cells. 2023 Jul 10;12(14):1820. doi: 10.3390/cells12141820.
Ferroptosis is a newly discovered iron-dependent form of regulated cell death driven by phospholipid peroxidation and associated with processes including iron overload, lipid peroxidation, and dysfunction of cellular antioxidant systems. Ferroptosis is found to be closely related to many diseases, including cancer at every stage. Epithelial-mesenchymal transition (EMT) in malignant tumors that originate from epithelia promotes cancer-cell migration, invasion, and metastasis by disrupting cell-cell and cell-cell matrix junctions, cell polarity, etc. Recent studies have shown that ferroptosis appears to share multiple initiators and overlapping pathways with EMT in cancers and identify ferroptosis as a potential predictor of various cancer grades and prognoses. Cancer metastasis involves multiple steps, including local invasion of cancer cells, intravasation, survival in circulation, arrest at a distant organ site, extravasation and adaptation to foreign tissue microenvironments, angiogenesis, and the formation of "premetastatic niche". Numerous studies have revealed that ferroptosis is closely associated with cancer metastasis. From the cellular perspective, ferroptosis has been implicated in the regulation of cancer metastasis. From the molecular perspective, the signaling pathways activated during the two events interweave. This review briefly introduces the mechanisms of ferroptosis and discusses how ferroptosis is involved in cancer progression, including EMT, cancer angiogenesis, invasion, and metastasis.
铁死亡是一种新发现的铁依赖性细胞死亡形式，由脂质过氧化驱动，并与包括铁过载、脂质过氧化和细胞抗氧化系统功能障碍在内的多种过程相关。铁死亡与许多疾病密切相关，包括各个阶段的癌症。起源于上皮组织的恶性肿瘤中的上皮间质转化（EMT）通过破坏细胞-细胞和细胞-细胞基质连接、细胞极性等，促进癌细胞的迁移、侵袭和转移。最近的研究表明，铁死亡似乎与癌症中的 EMT 具有多个共同的启动子和重叠途径，并将铁死亡鉴定为各种癌症分级和预后的潜在预测因子。癌症转移涉及多个步骤，包括癌细胞的局部侵袭、血管内渗透、在循环中的存活、在远处器官部位的停滞、血管外渗和适应外来组织微环境、血管生成以及“前转移龛”的形成。大量研究表明铁死亡与癌症转移密切相关。从细胞角度看，铁死亡参与了癌症转移的调控。从分子角度看，两个事件中激活的信号通路相互交织。本文简要介绍了铁死亡的机制，并讨论了铁死亡如何参与癌症进展，包括 EMT、癌症血管生成、侵袭和转移。
