The Critical Role of Ferroptosis in Hepatocellular Carcinoma

Fan, Ping; Lin, Xiaoyang; Hao, Liping; Wang, Ting; Song, Haiyan; Wang, Rui

doi:10.3389/fcell.2022.882571

Cited by 16 publications

(21 citation statements)

References 122 publications

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“…Despite the bumps along the way, an important breakthrough has been made that offers hope for the treatment of advanced gastric cancer patients; however, despite their impressive efficacy, treatment failure, drug resistance, and recurrence remain common [ 48 , 49 ]. Numerous studies have linked ferroptosis to the death of tumorigenic cells such as hepatocellular carcinoma, glioma, non-small cell lung cancer, and breast cancer [ 14 , 50 , 51 , 52 , 53 ]. As a result, targeting ferroptosis could be a novel approach to cancer treatment [ 54 ]; however, there are still relatively few studies on the role of ferroptosis in gastric cancer, especially the potential regulatory mechanisms in relation to TME characteristics, immunotherapy response, and prognosis, which remain to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

Zhou

Lan

et al. 2022

IJMS

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Ferroptosis is a relatively new form of programmed cell death, which can enhance the efficacy of tumor immunotherapy by regulating the tumor microenvironment (TME). In the face of the dilemma of a great difference in the efficacy of immunotherapy for gastric cancer (GC) patients, the exploration of ferroptosis may assist us in predicting immunotherapy efficacy prior to treatment. The potential role of ferroptosis in TME still needs further elucidation. Based on ferroptosis-related genes (FRGs), we systematically evaluated ferroptosis molecular subtypes in gastric cancer. Additionally, the association between these molecular subtypes and the characteristics of TME was examined. A ferroptosis score was constructed to further explore the predictive efficacy of ferroptosis on the immunotherapy response in gastric cancer. There were also 32 other cancers that were evaluated. Three molecular subtypes of ferroptosis in gastric cancer were identified. The three immunophenotypes of tumor immune inflamed, immune excluded, as well as immune desert were mostly in agreement with the TME features of these three subtypes. The individual tumor genetic variation, TME characteristics, immunotherapy response, and prognosis could be assessed by a ferroptosis score. High ferroptosis scores in gastric cancer suggest stromal activation and immunosuppression. It is noted that tumors with a low ferroptosis score are characterized by extensive tumor mutations as well as an immune activation, which are associated with an enhanced immunotherapy response and an improved prognosis. This study reveals that ferroptosis plays an integral role in the regulation of the tumor immune microenvironment. The ferroptosis score may serve as an independent prognostic factor for GC and will deepen our understanding of the TME infiltration mechanisms as well as lead to more rational immunotherapy regimens.

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Section: Discussionmentioning

confidence: 99%

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

Zhou

Lan

et al. 2022

IJMS

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“…Despite the all increasing importance of ferroptosis, there are no data on a possible interplay between ferroptosis, autophagy and apoptosis in HCC. The role of ferroptosis in HCC initiation and progression has been extensively reviewed [ 472 , 473 ].…”

Section: Interplay Between Apoptosis and Autophagymentioning

confidence: 99%

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

2023

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The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways that are critical for cell survival or death. The balance between apoptosis and autophagy regulates liver cell turnover and maintains intracellular homeostasis. However, the balance is often dysregulated in many cancers, including HCC. Autophagy and apoptosis pathways may be either independent or parallel or one may influence the other. Autophagy may either inhibit or promote apoptosis, thus regulating the fate of the liver cancer cells. In this review, a concise overview of the pathogenesis of HCC is presented, with emphasis on new developments, including the role of endoplasmic reticulum stress, the implication of microRNAs and the role of gut microbiota. The characteristics of HCC associated with a specific liver disease are also described and a brief description of autophagy and apoptosis is provided. The role of autophagy and apoptosis in the initiation, progress and metastatic potential is reviewed and the experimental evidence indicating an interplay between the two is extensively analyzed. The role of ferroptosis, a recently described specific pathway of regulated cell death, is presented. Finally, the potential therapeutic implications of autophagy and apoptosis in drug resistance are examined.

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“…Opening of mPTP depletes the ion gradient and drives ATP synthesis, resulting in energy deficiency and necroptosis [35]. Another form of proinflammatory programmed cell death, ferroptosis, is characterized by cytosolic iron overload and lipid peroxidation, generally without nuclear pyknosis, and featured smaller mitochondria and increased mitochondrial membrane density [36]. Autophagy is a noninflammatory catabolic pathway that also leads to cell death with intact but amorphous cell membranes.…”

Section: Difference and Crosstalk Between Pyroptosis And Other Forms ...mentioning

confidence: 99%

The regulatory role and therapeutic application of pyroptosis in musculoskeletal diseases

Wang

Feng

et al. 2022

Cell Death Discov.

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Pyroptosis is a controlled form of inflammatory cell death characterized by inflammasome activation, pore formation, and cell lysis. According to different caspases, pyroptosis can be divided into canonical, non-canonical, and other pathways. The role of pyroptosis in disease development has been paid more attention in recent years. The trigger factors of pyroptosis are often related to oxidative stress and proinflammatory substances, which coincide with the pathological mechanism of some diseases. Pyroptosis directly leads to cell lysis and death, and the release of cytosolic components and proinflammatory cytokines affects cell activity and amplifies the inflammatory response. All the above are involved in a series of basic pathological processes, such as matrix degradation, fibrosis, and angiogenesis. Since these pathological changes are also common in musculoskeletal diseases (MSDs), emerging studies have focused on the correlations between pyroptosis and MSDs in recent years. In this review, we first summarized the molecular mechanism of pyroptosis and extensively discussed the differences and crosstalk between pyroptosis, apoptosis, and necrosis. Next, we elaborated on the role of pyroptosis in some MSDs, including osteoarthritis, rheumatoid arthritis, osteoporosis, gout arthritis, ankylosing spondylitis, intervertebral disc degeneration, and several muscle disorders. The regulation of pyroptosis could offer potential therapeutic targets in MSDs treatment. Herein, the existing drugs and therapeutic strategies that directly or indirectly target pyroptosis pathway components have been discussed in order to shed light on the novel treatment for MSDs.

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The Critical Role of Ferroptosis in Hepatocellular Carcinoma

Cited by 16 publications

References 122 publications

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

The regulatory role and therapeutic application of pyroptosis in musculoskeletal diseases

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