Academic Journal
Regulation of SLC7A11 as an unconventional checkpoint in tumorigenesis through ferroptosis
| Title: | Regulation of SLC7A11 as an unconventional checkpoint in tumorigenesis through ferroptosis |
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| Authors: | Zhenyi Su, Yanqing Liu, Lin Wang, Wei Gu |
| Source: | Genes and Diseases, Vol 12, Iss 1, Pp 101254- (2025) |
| Publisher Information: | KeAi Communications Co., Ltd., 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine (General) LCC:Genetics |
| Subject Terms: | Ferroptosis, Metabolic checkpoint, SLC7A11, Stress, Targeted cancer therapy, Transcriptional regulation, Medicine (General), R5-920, Genetics, QH426-470 |
| More Details: | Although cell-cycle arrest, senescence, and apoptosis are well accepted as the classic barriers in tumorigenesis, recent studies indicate that metabolic regulation is equally important as a major checkpoint in cancer development. It is well accepted that ferroptosis, an iron-dependent programmed cell death, acts as a new type of tumor suppression mechanism tightly linked with numerous metabolic pathways. SLC7A11 is a transmembrane cystine/glutamate transporter protein that plays a vital role in controlling ferroptosis in vivo. The levels of SLC7A11 are dynamically regulated by various types of stresses, such as oxidative stress, nutrient deprivation, endoplasmic reticulum stress, radiation, oncogenic stress, DNA damage, and immune stress. SLC7A11 can be transcriptionally regulated by both activators such as ATF4, NRF2, and ETS1, and repressors including BACH1, p53, ATF3, and STAT1 during stress responses. Moreover, SLC7A11 activity and its protein stability and cellular localization are also modulated upon stress. Patients' data show that SLC7A11 is overexpressed in various types of human cancers, and higher levels of SLC7A11 predict poorer overall survival. Growing evidence also suggests that targeting SLC7A11 is a promising approach in cancer therapy by effectively inhibiting tumor proliferation, invasion, and metastasis, as well as counteracting cancer stem cells and overcoming chemoresistance. This review highlights the regulation of SLC7A11 as an unconventional checkpoint in tumorigenesis through modulating ferroptotic responses under various types of stress. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2352-3042 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2352304224000515; https://doaj.org/toc/2352-3042 |
| DOI: | 10.1016/j.gendis.2024.101254 |
| Access URL: | https://doaj.org/article/da58ba8726c94b8da6f77bfd76fbec25 |
| Accession Number: | edsdoj.58ba8726c94b8da6f77bfd76fbec25 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23523042 |
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| DOI: | 10.1016/j.gendis.2024.101254 |
| Published in: | Genes and Diseases |
| Language: | English |