Molecule Information

General Information of the Molecule (ID: Mol01067)

• Name: Renal carcinoma antigen NY-REN-56 (PFKFB3) ,Homo sapiens
• Synonyms: 6PF-2-K/Fru-2;6-P2ase 3; PFK/FBPase 3; 6PF-2-K/Fru-2;6-P2ase brain/placenta-type isozyme; Renal carcinoma antigen NY-REN-56; iPFK-2
• Molecule Type: Protein
• Gene Name: PFKFB3
• Gene ID: 5209
• Location: chr10:6144934-6254644[+]
• Sequence:
  MPLELTQSRVQKIWVPVDHRPSLPRSCGPKLTNSPTVIVMVGLPARGKTYISKKLTRYLN
  WIGVPTKVFNVGEYRREAVKQYSSYNFFRPDNEEAMKVRKQCALAALRDVKSYLAKEGGQ
  IAVFDATNTTRERRHMILHFAKENDFKAFFIESVCDDPTVVASNIMEVKISSPDYKDCNS
  AEAMDDFMKRISCYEASYQPLDPDKCDRDLSLIKVIDVGRRFLVNRVQDHIQSRIVYYLM
  NIHVQPRTIYLCRHGENEHNLQGRIGGDSGLSSRGKKFASALSKFVEEQNLKDLRVWTSQ
  LKSTIQTAEALRLPYEQWKALNEIDAGVCEELTYEEIRDTYPEEYALREQDKYYYRYPTG
  ESYQDLVQRLEPVIMELERQENVLVICHQAVLRCLLAYFLDKSAEEMPYLKCPLHTVLKL
  TPVAYGCRVESIYLNVESVCTHRERSEDAKKGPNPLMRRNSVTPLASPEPTKKPRINSFE
  EHVASTSAALPSCLPPEVPTQLPGQNMKGSRSSADSSRKH
• Function: Synthesis and degradation of fructose 2,6-bisphosphate.
• Uniprot ID: F263_HUMAN
• Ensembl ID: ENSG00000170525
• HGNC ID: HGNC:8874

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

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Tamoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: Hk2, PFkB3, ENO-1, and PkM-2 are the main enzymes of glycolysis and their expression is upregulated in TAMR cells. Hk2 is also involved in the activation of pro-survival autophagy. ENO-1 plays an important role by inhibiting apoptosis via downregulation of c-Myc. In mitochondria, PDk4 phosphorylation regulate Pyruvate dehydrogenase of PDC. NSD2 activates Hk-2, G6PD, and TIGAR expression and upregulates the PPP pathway. PPP produces NADH and Ribulose 5-Phosphate, a substrate for nucleotide biosynthesis. NADH reduces ROS and inhibits apoptosis. LDHA overexpression helps in aerobic glycolysis and indirectly promotes autophagy. To reduce the concentration of lactate in the cells, MCT expression is increased, which facilitates the efflux of lactate and cell survival.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

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: 1.81E-53; Fold-change: -1.17E+00; Z-score: -1.18E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.82E-05; Fold-change: -3.47E-01; Z-score: -3.31E-01

References

• Ref 1: 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.