Ferroptosis in Cancer Progression

Abstract

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.

Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

“…Hallmarks of cancer metabolism also include elevated iron requirements that under oxidative stress make cancer cells more susceptible to ferroptosis as compared to their normal counterparts. In addition, ferroptosis is regulated by numerous tumor-related genes and signaling pathways [ 57 , 58 ]. Several mechanisms involved in ferroptosis, including system Xc-, GPX4, lipid peroxidation, and GSH metabolism, mediate biological processes such as oxidative stress and iron overload and appear to be dysregulated in many cancer types [ 59 , 60 , 61 , 62 ].…”

GPX4 is a potential diagnostic and therapeutic biomarker associated with diffuse large B lymphoma cell proliferation and B cell immune infiltration

“…More and more evidence shows that ferroptosis disorder plays an important role in the development, recurrence and occurrence of multiple cancers, including DLBCL [ 3 , 4 ]. Besides, ferroptosis's imbalance is considered a valuable biomarker for the prognosis and diagnosis of DLBCL [ 5 ].…”

Metabolic dysfunction-associated steatotic liver disease: ferroptosis related mechanisms and potential drugs

“…The main factors contributing to the development of ferroptosis include abnormal iron metabolism or excessive iron intake, oxidation of unsaturated fatty acids, and impairment of antioxidant repair mechanisms (Li J. et al, 2020). Recently, ferroptosis has gained considerable attention in medical research due to its involvement in various conditions such as cancer, diabetes, cardio-cerebrovascular disease, and liver disease (Cheng et al, 2023;Miao et al, 2023;Zhang et al, 2023). Importantly, existing evidence suggests an interrelation between metabolic diseases, fatty liver, and ferroptosis, with the latter playing a crucial role in their pathogenesis.…”