System Xc−: a key regulatory target of ferroptosis in cancer

Liu, Man-Ru; Zhu, Wentao; Pei, Dong‐Sheng

doi:10.1007/s10637-021-01070-0

Cited by 128 publications

(89 citation statements)

References 86 publications

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“…GSH can be used as an electron donor to convert toxic phospholipid peroxide into non-toxic phosphatidyl alcohol oxidized glutathione under the action of GPX ( Bridges et al, 2011 ). Drugs such as RSL3 ( Yagoda et al, 2007 ) and hexamethylmelamine ( Liu et al, 2021 ), or interference with GPX4 expression ( Lin et al, 2018 ) can induce and promote ferroptosis. Moreover, this process can be induced by consumption GSH that will prevent GPX4 to lose its effect ( Yant et al, 2003 ; Li et al, 2020 ).…”

Section: Rcds and The Molecular Mechanismmentioning

confidence: 99%

Regulated Cell Death in Urinary Malignancies

Nie

Chen

Gao

et al. 2021

Front. Cell Dev. Biol.

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Urinary malignancies refer to a series of malignant tumors that occur in the urinary system and mainly include kidney, bladder, and prostate cancers. Although local or systemic radiotherapy and chemotherapy, immunotherapy, castration therapy and other methods have been applied to treat these diseases, their high recurrence and metastasis rate remain problems for patients. With in-depth research on the pathogenesis of urinary malignant tumors, this work suggests that regulatory cell death (RCD) plays an important role in their occurrence and development. These RCD pathways are stimulated by various internal and external environmental factors and can induce cell death or permit cell survival under the control of various signal molecules, thereby affecting tumor progression or therapeutic efficacy. Among the previously reported RCD methods, necroptosis, pyroptosis, ferroptosis, and neutrophil extracellular traps (NETs) have attracted research attention. These modes transmit death signals through signal molecules, such as cysteine-aspartic proteases (caspase) family and tumor necrosis factor-α (TNF-α) that have a wide and profound influence on tumor proliferation or death and even change the sensitivity of tumor cells to therapy. This review discussed the effects of necroptosis, pyroptosis, ferroptosis, and NETs on kidney, bladder and prostate cancer and summarized the latest research and achievements in these fields. Future directions and possibility of improving the denouement of urinary system tumors treatment by targeting RCD therapy were also explored.

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Section: Rcds and The Molecular Mechanismmentioning

confidence: 99%

Regulated Cell Death in Urinary Malignancies

Nie

Chen

Gao

et al. 2021

Front. Cell Dev. Biol.

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“…Its morphological characteristics are shrinkage of cell volume and increase of mitochondrial membrane density. The main feature of this process is the accumulation of iron-dependent lethal lipid ROS rather than cell death in the form of apoptosis [ 92 ]. Specifically, ferroptosis is due to the failure of the membrane lipid repair enzyme-glutathione peroxidase (GPX4), resulting in the accumulation of reactive oxygen radicals (ROS) on membrane lipids, and this accumulation process requires the participation of ions [ 93 ].…”

Section: Pyroptosis In Cancer Metastasismentioning

confidence: 99%

Non-coding RNAs in necroptosis, pyroptosis and ferroptosis in cancer metastasis

et al. 2021

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Distant metastasis is the main cause of death for cancer patients. Recently, the newly discovered programmed cell death includes necroptosis, pyroptosis, and ferroptosis, which possesses an important role in the process of tumor metastasis. At the same time, it is widely reported that non-coding RNA precisely regulates programmed death and tumor metastasis. In the present review, we summarize the function and role of necroptosis, pyrolysis, and ferroptosis involving in cancer metastasis, as well as the regulatory factors, including non-coding RNAs, of necroptosis, pyroptosis, and ferroptosis in the process of tumor metastasis.

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“…The amino acid antiporter system Xc-mediates the exchange of extracellular cystine and intracellular glutamate across the plasma membrane and is important for the synthesis of GSH, which prevents lipid peroxidation and protects cells against lipid peroxidation [ 33 ]. Actually, the activity of system Xc-usually positively correlates with the expression level of its light chain encoded by Slc7a11 [ 34 ].…”

Section: Resultsmentioning

confidence: 99%