Molecule Information

General Information of the Molecule (ID: Mol04048)

• Name: Monocarboxylate transporter 4 (MCT4) ,Homo sapiens
• Synonyms: Solute carrier family 16 member 3
• Molecule Type: Protein
• Gene Name: SLC16A3
• Gene ID: 9123
• Location: chr17:82217934-82261129[+]
• Sequence:
  MGGAVVDEGPTGVKAPDGGWGWAVLFGCFVITGFSYAFPKAVSVFFKELIQEFGIGYSDT
  AWISSILLAMLYGTGPLCSVCVNRFGCRPVMLVGGLFASLGMVAASFCRSIIQVYLTTGV
  ITGLGLALNFQPSLIMLNRYFSKRRPMANGLAAAGSPVFLCALSPLGQLLQDRYGWRGGF
  LILGGLLLNCCVCAALMRPLVVTAQPGSGPPRPSRRLLDLSVFRDRGFVLYAVAASVMVL
  GLFVPPVFVVSYAKDLGVPDTKAAFLLTILGFIDIFARPAAGFVAGLGKVRPYSVYLFSF
  SMFFNGLADLAGSTAGDYGGLVVFCIFFGISYGMVGALQFEVLMAIVGTHKFSSAIGLVL
  LMEAVAVLVGPPSGGKLLDATHVYMYVFILAGAEVLTSSLILLLGNFFCIRKKPKEPQPE
  VAAAEEEKLHKPPADSGVDLREVEHFLKAEPEKNGEVVHTPETSV
• Function: Proton-dependent transporter of monocarboxylates such as L- lactate and pyruvate (PubMed:11101640, PubMed:23935841, PubMed:31719150). Plays a predominant role in L-lactate efflux from highly glycolytic cells (By similarity). .
• Uniprot ID: MOT4_HUMAN
• Ensembl ID: ENSG00000141526
• HGNC ID: HGNC:10924

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

Approved Drug(s) 2 drug(s) in total

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Here we showed that exposure to chemotherapeutic drug etoposide induces an exacerbation of ROS production which activates HIF-1-mediated the metabolic reprogramming toward increased glycolysis and lactate production in non-small cell lung cancer.

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

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

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Cancer-associated fibroblasts; Pancreas; Homo sapiens (Human); N.A.
• Mechanism Description: Shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects.

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

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects.

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

• Metabolic Type: Glucose metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: BALB/c mice injected with PANC-1 cells; BALB/c mice injected with PANC-1 cells plus CAFs; Mice
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects.

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

Isoarnebin 4

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

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

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Sensitive Drug: Isoarnebin 4
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1-CM-enhanced WI-38 cells; Pancreas; Homo sapiens (Human); CVCL_0579
• In Vitro Model: Primary cancer-associated fibroblasts; Pancreas; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects.

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

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Sensitive Drug: Isoarnebin 4
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: WI-38 cells; Fetal lung; Homo sapiens (Human); CVCL_0579
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects.

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

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Sensitive Drug: Isoarnebin 4
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: BALB/c mice injected with PANC-1 cells; BALB/c mice injected with PANC-1 cells plus CAFs; Mice
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects.

References

• Ref 1: Lactate-induced MRP1 expression contributes to metabolism-based etoposide resistance in non-small cell lung cancer cells. Cell Commun Signal. 2020 Oct 23;18(1):167.
• Ref 2: Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect. Phytomedicine. 2024 Jan;123:155214.