Molecule Information

General Information of the Molecule (ID: Mol04211)

• Name: N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) ,Homo sapiens
• Synonyms: N-6 adenine-specific DNA methyltransferase 1 (N6AMT1)
• Molecule Type: Protein

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 adenocarcinoma [ICD-11: 2C60.1] [1]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: MCF-7 TamR cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: T47D TamR cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: We discover, via bioinformatics analysis and clinical samples, that N6 adenine-specific DNA methyltransferase 1 (N6AMT1) is highly expressed in luminal breast cancer but downregulated in tamoxifen-resistant (TamR) BC cells. ChIP-qPCR and luciferase reporter assays showed that FOXA1 binds to the N6AMT1 promoter and enhances its transcription. In TamR models, FOXA1 and N6AMT1 are downregulated, increasing p110alpha protein levels (but not mRNA), phospho-AKT levels, and tamoxifen resistance. In vivo, N6AMT1 overexpression enhanced tamoxifen sensitivity, while knockdown reduced it; this sensitivity could be restored with the p110alpha inhibitor A66.

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

A66

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: A66
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: MCF-7 TamR cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: T47D TamR cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: We discover, via bioinformatics analysis and clinical samples, that N6 adenine-specific DNA methyltransferase 1 (N6AMT1) is highly expressed in luminal breast cancer but downregulated in tamoxifen-resistant (TamR) BC cells. ChIP-qPCR and luciferase reporter assays showed that FOXA1 binds to the N6AMT1 promoter and enhances its transcription. In TamR models, FOXA1 and N6AMT1 are downregulated, increasing p110alpha protein levels (but not mRNA), phospho-AKT levels, and tamoxifen resistance. In vivo, N6AMT1 overexpression enhanced tamoxifen sensitivity, while knockdown reduced it; this sensitivity could be restored with the p110alpha inhibitor A66.

References

• Ref 1: Reversal of endocrine resistance via N6AMT1-NEDD4L pathway-mediated p110alpha degradation. Oncogene. 2025 Mar;44(8):530-544.