Molecule Information

General Information of the Molecule (ID: Mol04143)

• Name: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) ,Homo sapiens
• Synonyms: 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
• 3D-structure: PDB ID: 6HVI; Classification: Transferase; Method: X-ray diffraction; Resolution: 1.96 Å
• Function: Catalyzes both the 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

  MRAP: Metabolic Reprogramming via Altered Pathways

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Sunitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB3 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 769-P cells; Kidney; Homo sapiens (Human); CVCL_1050
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB4 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB5 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB6 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki-2 cells; Kidney; Homo sapiens (Human); CVCL_0235
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB7 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hk-2 cells; Kidney; Homo sapiens (Human); CVCL_0302
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB8 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Tamoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [2]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; M2000T
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7/TamR cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Annexin V-propidium iodide staining assay
• Mechanism Description: Aerobic glycolysis, a metabolic process, has been implicated in chemotherapeutic resistance. In this study, we demonstrate that elevated glycolysis plays a central role in TAM resistance and can be effectively targeted and overcome by Rg3. Mechanistically, we observed upregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key mediator of glycolysis, in TAM-resistant MCF-7/TamR and T-47D/TamR cells. Crucially, PFKFB3 is indispensable for the synergistic effect of TAM and Rg3 combination therapy, which suppresses cell proliferation and glycolysis in MCF-7/TamR and T-47D/TamR cells, both in vitro and in vivo. Moreover, overexpression of PFKFB3 in MCF-7 cells mimicked the TAM resistance phenotype. Importantly, combination treatment significantly reduced TAM-resistant MCF-7 cell proliferation in an in vivo model.

References

• Ref 1: Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification. Eur J Med Res. 2024 Apr 15;29(1):236.
• Ref 2: Ginsenoside Rg3 overcomes tamoxifen resistance through inhibiting glycolysis in breast cancer cells. Cell Biol Int. 2024 Apr;48(4):496-509.