Molecule Information

General Information of the Molecule (ID: Mol04105)

• Name: Enolase 2 (ENO2) ,Homo sapiens
• Synonyms: 2-phospho-D-glycerate hydro-lyase; Enolase 2; Neural enolase; Neuron-specific enolase
• Molecule Type: Protein
• Gene Name: ENO2
• Gene ID: 2026
• Location: chr12:6913745-6923698[+]
• Sequence:
  MSIEKIWAREILDSRGNPTVEVDLYTAKGLFRAAVPSGASTGIYEALELRDGDKQRYLGK
  GVLKAVDHINSTIAPALISSGLSVVEQEKLDNLMLELDGTENKSKFGANAILGVSLAVCK
  AGAAERELPLYRHIAQLAGNSDLILPVPAFNVINGGSHAGNKLAMQEFMILPVGAESFRD
  AMRLGAEVYHTLKGVIKDKYGKDATNVGDEGGFAPNILENSEALELVKEAIDKAGYTEKI
  VIGMDVAASEFYRDGKYDLDFKSPTDPSRYITGDQLGALYQDFVRDYPVVSIEDPFDQDD
  WAAWSKFTANVGIQIVGDDLTVTNPKRIERAVEEKACNCLLLKVNQIGSVTEAIQACKLA
  QENGWGVMVSHRSGETEDTFIADLVVGLCTGQIKTGAPCRSERLAKYNQLMRIEEELGDE
  ARFAGHNFRNPSVL
• 3D-structure: PDB ID: 3UJR; Classification: Lyase; Method: X-ray diffraction; Resolution: 1.40 Å
• Function: Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium- dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity). .
• Uniprot ID: ENOG_HUMAN
• Ensembl ID: ENSG00000111674
• HGNC ID: HGNC:3353

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) 1 drug(s) in total

Bevacizumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Bevacizumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vivo Model: 6-to 8-week-old female NOD/SCID mice, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Here, we found that high levels of ENO2 expression and ENO2-related neuroendocrine differentiation were associated with resistance to antiangiogenic therapy in CRC. Notably, the ENO2-derived PEP was responsible for ENO2-mediated resistance to antiangiogenic therapy in CRC, and PEP enhanced beta-catenin Lys49 acetylation by selectively inhibiting histone deacetylase 1 (HDAC1) activity.

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Bevacizumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: 4-to 6-week-old female BALB/c nude mice, with HCT116vector, HCT116ENO2, HCT116shNC and HCT116shENO2, Rego-resistant SW620 or Bev-resistant HCT116 cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Here, we found that high levels of ENO2 expression and ENO2-related neuroendocrine differentiation were associated with resistance to antiangiogenic therapy in CRC. Notably, the ENO2-derived PEP was responsible for ENO2-mediated resistance to antiangiogenic therapy in CRC, and PEP enhanced beta-catenin Lys49 acetylation by selectively inhibiting histone deacetylase 1 (HDAC1) activity.

References

• Ref 1: ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy. Nat Metab. 2023 Oct;5(10):1765-1786.