Introduction of SLC7A11
SLC7A11 (solute carrier family 7 member 11), also known as system Xc-, xCT or CCBR1, is a cystine/glutamate exchanger encoded by the SLC7A11 gene. SLC7A11 is an important member of SLC7 family which is divided into two major subgroups, cationic amino acid transporters (CATs, SLC7A1-4) and glycoprotein-associated amino acid transporters (gpaATs, SLC7A5-11), also called catalytic chains of the hetero(di)meric amino acid transporters (HATs). The Na+-independent heterodimeric SLC7A11 transporter comprises two chains, a specific light chain (xCT) and a heavy chain (4F2), which are linked by a disulfide bridge. The xCT chain is predicted to possess 12 transmembrane (TM) segments, while the 4F2 chain appears to be highly conserved among transporters. The SLC7A11 gene is widely expressed in central nervous and peripheral tissues, including the basolateral amygdala, prefrontal cortex, spinal cord, pancreas, and glioma cells. SLC7A11 gene is mapped to the chromosome 4q28-q32.
|Basic Information of SLC7A11|
|Protein Name||Cystine/glutamate transporter|
|Organism||Homo sapiens (Human)|
Function of SLC7A11 Membrane Protein
As an important member of HATs subgroup, SLC7A11 functions in uptake of anionic amino acids with high specificity for anionic form of cystine and glutamate with sodium-independence and high-affinity. The ability to promote glutathione biosynthesis helps SLC7A11 to play roles in protection from oxidative stress and ferroptotic cell death. SLC7A11 has been detected to be overexpressed in various cancers, including non-small cell lung cancer (NSCLC) and oral cancer, suggesting its roles in supporting tumor progression. It is documented that SLC7A11 adjusts the cystine content of melanocytes, then regulates pheomelanin synthesis, ultimately affects the proportion of total melanin, changing mammalian coat colour. Moreover, SLC7A11 activity is decreased in the nucleus accumbens core (NAcc) region of the brains when exposed to cocaine, resulting in a decrease in basal, extra synaptic glutamate levels of the brains of cocaine-withdrawn rats. So SLC7A11 is recognized as a novel target for medication that could prevent cocaine relapse. Recent studies have shown that impaired SLC7A11 transporters may result in a disruption in glutamate homeostasis and lead to a variety of CNS disorders, such as schizophrenia, gliomas, amyotrophic lateral sclerosis, Alzheimer's, Parkinson's disease and neurotoxins.
Fig.1 SLC7A11 can promote the oxidative stress responses and inhibit ferroptosis. (Koppula, 2018)
Application of SLC7A11 Membrane Protein in Literature
The authors used small interfering RNA (siRNA) to interfere SLC7A11 gene expression and explored its function in the expression of melanogenesis-related genes (MITF, MC1R, Agouti, CREB1, and SLC24A5) in rabbit skin fibroblasts (RAB-9).
This article demonstrated that on the cytoplasmic membrane of non-small cell lung cancer (NSCLC), xCT presents high expression, which is correlated with advanced stage and predicted a worse 5-year survival. Furthermore, using sulfasalazine targeting xCT transport activity can decrease cell proliferation and invasion in vitro and in vivo.
The review highlighted that SLC7A11 not only promotes cystine uptake and glutathione biosynthesis but also plays key roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells, indicating that SLC7A11 may be a new therapeutic target for cancer treatment.
The authors used bioinformatic analysis and a tissue microarray to validate the expression and clinical significance of SLC7A11 in liver cancer, and they demonstrated that SLC7A11 presents high expression in liver cancer with no association with clinical parameters, indicating that SLC7A11 might be an independent prognostic factor for liver cancer patients.
The review utilized a hereditary tyrosinemia model (Fah-/- mice) which conditionally suffered severe liver injury because of the destruction of fumarylacetoacetate hydrolase (FAH) expression to discover the upstream regulators and important signaling pathways in regenerating hepatocytes, and they revealed that Slc7a11 was upregulated during liver regeneration.
SLC7A11 Preparation Options
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