Molecule Information

General Information of the Molecule (ID: Mol00079)

• Name: Solute carrier family 2 member 1 (SLC2A1) ,Homo sapiens
• Synonyms: Glucose transporter type 1; erythrocyte/brain; GLUT-1; HepG2 glucose transporter; GLUT1
• Molecule Type: Protein
• Gene Name: SLC2A1
• Gene ID: 6513
• Location: chr1:42925353-42958893[-]
• Sequence:
  MEPSSKKLTGRLMLAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWVHRYGESILPTT
  LTTLWSLSVAIFSVGGMIGSFSVGLFVNRFGRRNSMLMMNLLAFVSAVLMGFSKLGKSFE
  MLILGRFIIGVYCGLTTGFVPMYVGEVSPTALRGALGTLHQLGIVVGILIAQVFGLDSIM
  GNKDLWPLLLSIIFIPALLQCIVLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTHD
  LQEMKEESRQMMREKKVTILELFRSPAYRQPILIAVVLQLSQQLSGINAVFYYSTSIFEK
  AGVQQPVYATIGSGIVNTAFTVVSLFVVERAGRRTLHLIGLAGMAGCAILMTIALALLEQ
  LPWMSYLSIVAIFGFVAFFEVGPGPIPWFIVAELFSQGPRPAAIAVAGFSNWTSNFIVGM
  CFQYVEQLCGPYVFIIFTVLLVLFFIFTYFKVPETKGRTFDEIASGFRQGGASQSDKTPE
  ELFHPLGADSQV
• 3D-structure: PDB ID: 6THA; Classification: Membrane protein; Method: X-ray diffraction; Resolution: 2.40 Å
• Function: Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake. Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses. Most important energy carrier of the brain: present at the blood-brain barrier and assures the energy-independent, facilitative transport of glucose into the brain. In association with BSG and NXNL1, promotes retinal cone survival by increasing glucose uptake into photoreceptors.
• Uniprot ID: GTR1_HUMAN
• Ensembl ID: ENSG00000117394
• HGNC ID: HGNC:11005

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

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  MRAP: Metabolic Reprogramming via Altered Pathways

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 7 drug(s) in total

Irinotecan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Irinotecan
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.33E-08; Fold-change: 5.47E-01; Z-score: 5.83E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Adrenergic signaling in cardiomyocytes; Activation; hsa04261
• In Vivo Model: Female SCID mice of 4-week-old, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Irinotecan
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.33E-08; Fold-change: 5.47E-01; Z-score: 5.83E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Adrenergic signaling in cardiomyocytes; Activation; hsa04261
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Mechanism Description: Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.33E-08; Fold-change: 5.47E-01; Z-score: 5.83E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Adrenergic signaling in cardiomyocytes; Activation; hsa04261
• In Vivo Model: Female SCID mice of 4-week-old, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.33E-08; Fold-change: 5.47E-01; Z-score: 5.83E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Adrenergic signaling in cardiomyocytes; Activation; hsa04261
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Mechanism Description: Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.33E-08; Fold-change: 5.47E-01; Z-score: 5.83E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Adrenergic signaling in cardiomyocytes; Activation; hsa04261
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Mechanism Description: Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.33E-08; Fold-change: 5.47E-01; Z-score: 5.83E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Adrenergic signaling in cardiomyocytes; Activation; hsa04261
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Mechanism Description: Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic cancer
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.68E-16; Fold-change: 2.62E-01; Z-score: 1.07E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Adrenergic signaling in cardiomyocytes; Activation; hsa04261
• In Vivo Model: Female SCID mice of 4-week-old, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression.

Methotrexate

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Liver cancer [ICD-11: 2C12.6] [2]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Methotrexate
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Liver cancer
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.55E-07; Fold-change: -3.93E-01; Z-score: -5.40E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Curcumin mediated the amputation of chemoresistance by repressing the hyperglycolytic behavior of malignant cells via modulated expression of metabolic enzymes (HkII, PFk1, GAPDH, PkM2, LDH, SDH, IDH, and FASN), transporters (GLUT-1, MCT-1, and MCT-4), and their regulators. Along altered constitution of extracellular milieu, these molecular changes culminated into improved drug accumulation, chromatin condensation, and induction of cell death.

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Liver cancer [ICD-11: 2C12.6] [2]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Liver cancer
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.55E-07; Fold-change: -3.93E-01; Z-score: -5.40E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Curcumin mediated the amputation of chemoresistance by repressing the hyperglycolytic behavior of malignant cells via modulated expression of metabolic enzymes (HkII, PFk1, GAPDH, PkM2, LDH, SDH, IDH, and FASN), transporters (GLUT-1, MCT-1, and MCT-4), and their regulators. Along altered constitution of extracellular milieu, these molecular changes culminated into improved drug accumulation, chromatin condensation, and induction of cell death.

Tamoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [ICD-11: 2C60.3] [3]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.10E-51; Fold-change: 1.07E-01; Z-score: 1.63E+01
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Immunohistochemical assay
• Mechanism Description: Overexpression of GLUT1 has been reported in aggressive and malignant breast cancer and has been correlated with the poor prognosis. Increased expression of GLUT1 in the TAMR cells compared to the TAM-sensitive cells. knockdown of GLUT1 in TAMR MCF-7 cells resulted in increased expression of p62 protein and decreased levels of LC3B-II, leading to autophagy and cells becoming sensitive to TAM.

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] [4]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR218-Glut1 signaling pathway; Regulation; N.A.
• In Vitro Model: EJ cells; Bladder; Homo sapiens (Human); CVCL_UI82
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.22E-08; Fold-change: 2.12E-03; Z-score: 1.22E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.44E-12; Fold-change: 7.94E-02; Z-score: 3.55E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 6.79E-04; Fold-change: 1.78E-01; Z-score: 1.38E+00

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.10E-51; Fold-change: 3.16E-01; Z-score: 9.69E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.11E-14; Fold-change: 3.90E-01; Z-score: 1.13E+00

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: 1.00E-06; Fold-change: 1.07E+00; Z-score: 3.52E+00

References

• Ref 1: Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer. Cell Rep Med. 2023 Sep 19;4(9):101162.
• Ref 2: Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells. Front Oncol. 2021 Oct 6;11:738961. doi: 10.3389/fonc.2021.738961. eCollection 2021.
• Ref 3: Metabolic reprograming confers tamoxifen resistance in breast cancer. Chem Biol Interact. 2021 Sep 25;347:109602. doi: 10.1016/j.cbi.2021.109602. Epub 2021 Jul 28.
• Ref 4: MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1. Cell Physiol Biochem. 2017;41(3):921-932. doi: 10.1159/000460505. Epub 2017 Feb 20.