Molecule Information

General Information of the Molecule (ID: Mol00709)

• Name: Cystine/glutamate transporter (SLC7A11) ,Homo sapiens
• Synonyms: Amino acid transport system xc-; Calcium channel blocker resistance protein CCBR1; Solute carrier family 7 member 11; xCT
• Molecule Type: Protein
• Gene Name: SLC7A11
• Gene ID: 23657
• Location: chr4:138164097-138242349[-]
• Sequence:
  MVRKPVVSTISKGGYLQGNVNGRLPSLGNKEPPGQEKVQLKRKVTLLRGVSIIIGTIIGA
  GIFISPKGVLQNTGSVGMSLTIWTVCGVLSLFGALSYAELGTTIKKSGGHYTYILEVFGP
  LPAFVRVWVELLIIRPAATAVISLAFGRYILEPFFIQCEIPELAIKLITAVGITVVMVLN
  SMSVSWSARIQIFLTFCKLTAILIIIVPGVMQLIKGQTQNFKDAFSGRDSSITRLPLAFY
  YGMYAYAGWFYLNFVTEEVENPEKTIPLAICISMAIVTIGYVLTNVAYFTTINAEELLLS
  NAVAVTFSERLLGNFSLAVPIFVALSCFGSMNGGVFAVSRLFYVASREGHLPEILSMIHV
  RKHTPLPAVIVLHPLTMIMLFSGDLDSLLNFLSFARWLFIGLAVAGLIYLRYKCPDMHRP
  FKVPLFIPALFSFTCLFMVALSLYSDPFSTGIGFVITLTGVPAYYLFIIWDKKPRWFRIM
  SEKITRTLQIILEVVPEEDKL
• 3D-structure: PDB ID: 7EPZ; Classification: Membrane protein; Method: Electron microscopy; Resolution: 3.40 Å
• Function: Sodium-independent, high-affinity exchange of anionic amino acids with high specificity for anionic form of cystine and glutamate.
• Uniprot ID: XCT_HUMAN
• Ensembl ID: ENSG00000151012
• HGNC ID: HGNC:11059

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Ovarian clear cell carcinoma [ICD-11: 2C73.00] [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: Ovarian clear cell carcinoma [ICD-11: 2C73.00]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.27E-01; Fold-change: 1.23E-01; Z-score: 1.31E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caov-3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: HAC-2 cells; Ovary; Homo sapiens (Human); CVCL_8354
• In Vitro Model: RMG-1 cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: SKOV-3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: TOV21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: This study demonstrated that combined treatment with paclitaxel (PTX) and the xCT inhibitor sulfasalazine (SAS) significantly enhanced cytotoxicity more than the individual drugs did in OCCC cells. Treatment with PTX and SAS induced apoptosis more effectively than did individual drug treatments in the cells with significant generation of ROS.

Alectinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Alectinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ALK1903 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: DTP cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CellTiter-Glo 3D cell viability assay
• Mechanism Description: DTP cells evade ALK-TKI-induced ROS-mediated cell death through GPX4 activity. From these data showing elevated levels of ROS that arise through decreased levels of various antioxidant factors and decreased GSH synthesis, it might be expected that ROS-mediated cell death should occur in alectinib-induced DTP cells. However, DTP cells concurrently upregulated GPX4 protein, suggesting that ALK1903 DTP cells are able to evade ROS-mediated cell death by reducing ROS level in a GPX4-dependent manner.

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Bladder cancer [ICD-11: 2C94.0] [3]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: EJ/T24 cells; Bladder; Homo sapiens (Human); N.A.
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• Experiment for Molecule Alteration: Tissue array assay
• Experiment for Drug Resistance: Clonogenic survival assay
• Mechanism Description: Cisplatin resistance is mediated through increased expression of SLC7A11 and increased production of glutathione, Overexpression of microRNA 27a reduces levels of SLC7A11 and intracellular glutathione, and resensitises resistant cells to cisplatin, SLC7A11 is a key modulator of cisplatin resistance in bladder cancer cells.

Sulfasalazine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Ovarian clear cell carcinoma [ICD-11: 2C73.00] [1]

• Metabolic Type: Redox metabolism
• Sensitive Disease: Ovarian clear cell carcinoma [ICD-11: 2C73.00]
• Sensitive Drug: Sulfasalazine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caov-3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: HAC-2 cells; Ovary; Homo sapiens (Human); CVCL_8354
• In Vitro Model: RMG-1 cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: SKOV-3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: TOV21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: This study demonstrated that combined treatment with paclitaxel (PTX) and the xCT inhibitor sulfasalazine (SAS) significantly enhanced cytotoxicity more than the individual drugs did in OCCC cells. Treatment with PTX and SAS induced apoptosis more effectively than did individual drug treatments in the cells with significant generation of ROS.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Bladder cancer [ICD-11: 2C94]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bladder tissue
• The Specified Disease: Bladder cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.20E-03; Fold-change: 3.85E-01; Z-score: 8.97E-01

References

• Ref 1: Mechanism of Cell Death by Combined Treatment with an xCT Inhibitor and Paclitaxel: An Alternative Therapeutic Strategy for Patients with Ovarian Clear Cell Carcinoma. Int J Mol Sci. 2023 Jul 22;24(14):11781.
• Ref 2: Combined blockade of GPX4 and activated EGFR/HER3 bypass pathways inhibits the development of ALK-inhibitor-induced tolerant persister cells in ALK-fusion-positive lung cancer. Mol Oncol. 2025 Feb;19(2):519-539.
• Ref 3: Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11. Clin Cancer Res. 2014 Apr 1;20(7):1990-2000. doi: 10.1158/1078-0432.CCR-13-2805. Epub 2014 Feb 10.