Research progress on SLC7A11 in the regulation of cystine/cysteine metabolism in tumors (Review)

Abstract

Solute carrier family 7 member 11 (SLC7A11) is a major transporter regulating cysteine metabolism and is widely expressed in a variety of tumor cells. SLC7A11 plays an important role in the occurrence, development, invasion and metastasis of tumors by regulating the transport of cysteine in the tumor microenvironment. SLC7A11 is expected to become a new therapeutic target and prognostic indicator for the individualized treatment of patients. According to relevant research reports, SLC7A11 can predict the stages and metastasis of liver, breast and lung cancer. Therefore, an in-depth exploration of the role of SLC7A11 in tumors may be important for the screening, early diagnosis, treatment and prognosis of patients with tumors. The current review summarizes the research progress on SLC7A11 in liver cancer, lung cancer and other tumors on the basis of previous primary studies. In addition, the present review systematically elaborates on the three main aspects of SLC7A11 pathways in some tumors, the cancer-promoting mechanisms, and the therapeutic relationship between SLC7A11 and tumors. Finally, the present review aims to provide a reference for assessing whether SLC7A11 can be used as a prognostic indicator and treatment target for tumor patients, and the future research direction with regard to SLC7A11 in tumors. Contents1. Introduction 2. Structure and biological function of cysteine 3. Structure and function of SLC7A11 and its regulatory mechanism 4. SLC7A11 regulates the association between cysteine metabolism and tumors 5. Future prospects

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

“…On the other hand, domain-specific BETis appear to have fewer adverse effects and some have already been approved for clinical use ( Pérez-Salvia and Esteller, 2017 ; Petretich et al, 2020 ). BRD4 negatively regulates ferroptosis by activating xCT, repairing the DNA, and inducing senescence-associated secretory phenotype (SASP), a ferroptosis resistant cellular program ( Tasdemir et al, 2016 ; Sui et al, 2019 ; Lam et al, 2020 ; Tang et al, 2022 ). In addition, BRD4 promotes iron sequestration in ferritin to withhold it from pathogens, likely implicating this protein in nutritional immunity ( Sui et al, 2019 ).…”

WITHDRAWN:In vivoCRISPR screen definesSlc25a37as an organ-specific regulator of antioxidant metabolism in metastasis

“…For example, it was found that CRC liver and lymph node metastases had higher protein expression of the amino acid transporter SLC6A14 compared to adjacent healthy tissue (Bhutia et al, 2014), and that inhibition of SLC16A4 reduced invasion and growth of CRC tumors (Lu et al, 2022). Moreover, mRNA expression of the well-studied glutamate-cystine antiporter, SLC7A11 , was shown to predict the stages and metastasis of liver, breast, and lung cancers (Tang et al, 2022). Highlighting the importance of SLC transporters, it was found that the expression pattern changes of SLCs in cancer are more dramatic than that of protein kinases (César-Razquin et al, 2015).…”

The role of microRNAs in ferroptosis

“…As a part of the Xc − transporter, SLC7A11 also plays a significant role in the antioxidant system (Jyotsana et al, 2022). The study of Liu et al inhibited cardiac fibroblast-derived exon-miR-23a-3p by using the exosome inhibitor GW4869, and inhibition of miR-23a-3p resulted in upregulation of SLC7A11, thereby reducing ferroptosis in H9c2 cardiomyocytes and preventing continued development of atrial flutter (Liu D. et al, 2022). It suggests that miR-23a-3p inhibition increases intracellular cystine and GSH levels, thereby neutralizing ROS and treating atrial fibrillation.…”

“…In the absence of GPX4, FSP1 can be used as an oxidoreductase to inhibit ROS and alleviate ferroptosis. SLC7A11 is widely expressed in various tumor tissues, and plays a significant role in inhibiting ferroptosis during the occurrence and development of tumors by controlling cysteine transport (Tang et al, 2022). Sun et al found that the miR-34c-3p/SLC7A11 axis can potentiate erastin-induced ferroptosis in oral squamous cell carcinoma (Sun et al, 2022).…”