Molecule Information

General Information of the Molecule (ID: Mol04046)

• Name: Monocarboxylate transporter 1 (MCT1) ,Homo sapiens
• Synonyms: Solute carrier family 16 member 1
• Molecule Type: Protein
• Gene Name: SLC16A1
• Gene ID: 6566
• Location: chr1:112911847-112957593[-]
• Sequence:
  MPPAVGGPVGYTPPDGGWGWAVVIGAFISIGFSYAFPKSITVFFKEIEGIFHATTSEVSW
  ISSIMLAVMYGGGPISSILVNKYGSRIVMIVGGCLSGCGLIAASFCNTVQQLYVCIGVIG
  GLGLAFNLNPALTMIGKYFYKRRPLANGLAMAGSPVFLCTLAPLNQVFFGIFGWRGSFLI
  LGGLLLNCCVAGALMRPIGPKPTKAGKDKSKASLEKAGKSGVKKDLHDANTDLIGRHPKQ
  EKRSVFQTINQFLDLTLFTHRGFLLYLSGNVIMFFGLFAPLVFLSSYGKSQHYSSEKSAF
  LLSILAFVDMVARPSMGLVANTKPIRPRIQYFFAASVVANGVCHMLAPLSTTYVGFCVYA
  GFFGFAFGWLSSVLFETLMDLVGPQRFSSAVGLVTIVECCPVLLGPPLLGRLNDMYGDYK
  YTYWACGVVLIISGIYLFIGMGINYRLLAKEQKANEQKKESKEEETSIDVAGKPNEVTKA
  AESPDQKDTDGGPKEEESPV
• 3D-structure: PDB ID: 7YR5; Classification: Membrane protein; Method: Electron microscopy; Resolution: 3.63 Å
• Function: Bidirectional proton-coupled monocarboxylate transporter (PubMed:12946269, PubMed:32946811, PubMed:33333023). Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH (PubMed:12946269, PubMed:33333023). The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (By similarity). Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart (PubMed:32946811). Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition (PubMed:33333023). .
• Uniprot ID: MOT1_HUMAN
• Ensembl ID: ENSG00000155380
• HGNC ID: HGNC:10922

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

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Clinical Trial Drug(s) 1 drug(s) in total

CB839

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: Glutamine metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: CB839
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: PDAC patients; Homo Sapiens
• Experiment for Molecule Alteration: qPCR
• Mechanism Description: Metabolic pressures like glutamine deficiency lead to the emergence of an aggressive and poor prognostic reverse Warburg phenotype in PDAC. As the major fuel of this phenotype, lactate taken up by MCT1 maintains cellular redox homeostasis and thereby cell viability during critical shortages of glutamine supply. This also manifests in resistance against inhibitors of glutamine metabolism, thus limiting their usage in the clinic.

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

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: CB839
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A818-6 cells; Pancreas; Homo sapiens (Human); CVCL_3893
• In Vitro Model: T3M4 cells; Pancreas; Homo sapiens (Human); CVCL_4056
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Metabolic pressures like glutamine deficiency lead to the emergence of an aggressive and poor prognostic reverse Warburg phenotype in PDAC. As the major fuel of this phenotype, lactate taken up by MCT1 maintains cellular redox homeostasis and thereby cell viability during critical shortages of glutamine supply. This also manifests in resistance against inhibitors of glutamine metabolism, thus limiting their usage in the clinic.

Preclinical Drug(s) 1 drug(s) in total

V9302

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: Glutamine metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: V9302
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: PDAC patients; Homo Sapiens
• Experiment for Molecule Alteration: qPCR
• Mechanism Description: Metabolic pressures like glutamine deficiency lead to the emergence of an aggressive and poor prognostic reverse Warburg phenotype in PDAC. As the major fuel of this phenotype, lactate taken up by MCT1 maintains cellular redox homeostasis and thereby cell viability during critical shortages of glutamine supply. This also manifests in resistance against inhibitors of glutamine metabolism, thus limiting their usage in the clinic.

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

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: V9302
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A818-6 cells; Pancreas; Homo sapiens (Human); CVCL_3893
• In Vitro Model: T3M4 cells; Pancreas; Homo sapiens (Human); CVCL_4056
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Metabolic pressures like glutamine deficiency lead to the emergence of an aggressive and poor prognostic reverse Warburg phenotype in PDAC. As the major fuel of this phenotype, lactate taken up by MCT1 maintains cellular redox homeostasis and thereby cell viability during critical shortages of glutamine supply. This also manifests in resistance against inhibitors of glutamine metabolism, thus limiting their usage in the clinic.

References

• Ref 1: Monocarboxylate Transporter-1 (MCT1)-Mediated Lactate Uptake Protects Pancreatic Adenocarcinoma Cells from Oxidative Stress during Glutamine Scarcity Thereby Promoting Resistance against Inhibitors of Glutamine Metabolism. Antioxidants (Basel). 2023 Sep 30;12(10):1818.