Molecule Information

General Information of the Molecule (ID: Mol04109)

• Name: Forkhead box M1 (FOXM1) ,Homo sapiens
• Synonyms: Forkhead-related protein FKHL16; Hepatocyte nuclear factor 3 forkhead homolog 11; M-phase phosphoprotein 2; MPM-2 reactive phosphoprotein 2; Transcription factor Trident; Winged-helix factor from INS-1 cells
• Molecule Type: Protein
• Gene Name: FOXM1
• Gene ID: 2305
• Location: chr12:2857680-2877174[-]
• Sequence:
  MKTSPRRPLILKRRRLPLPVQNAPSETSEEEPKRSPAQQESNQAEASKEVAESNSCKFPA
  GIKIINHPTMPNTQVVAIPNNANIHSIITALTAKGKESGSSGPNKFILISCGGAPTQPPG
  LRPQTQTSYDAKRTEVTLETLGPKPAARDVNLPRPPGALCEQKRETCADGEAAGCTINNS
  LSNIQWLRKMSSDGLGSRSIKQEMEEKENCHLEQRQVKVEEPSRPSASWQNSVSERPPYS
  YMAMIQFAINSTERKRMTLKDIYTWIEDHFPYFKHIAKPGWKNSIRHNLSLHDMFVRETS
  ANGKVSFWTIHPSANRYLTLDQVFKPLDPGSPQLPEHLESQQKRPNPELRRNMTIKTELP
  LGARRKMKPLLPRVSSYLVPIQFPVNQSLVLQPSVKVPLPLAASLMSSELARHSKRVRIA
  PKVLLAEEGIAPLSSAGPGKEEKLLFGEGFSPLLPVQTIKEEEIQPGEEMPHLARPIKVE
  SPPLEEWPSPAPSFKEESSHSWEDSSQSPTPRPKKSYSGLRSPTRCVSEMLVIQHRERRE
  RSRSRRKQHLLPPCVDEPELLFSEGPSTSRWAAELPFPADSSDPASQLSYSQEVGGPFKT
  PIKETLPISSTPSKSVLPRTPESWRLTPPAKVGGLDFSPVQTSQGASDPLPDPLGLMDLS
  TTPLQSAPPLESPQRLLSSEPLDLISVPFGNSSPSDIDVPKPGSPEPQVSGLAANRSLTE
  GLVLDTMNDSLSKILLDISFPGLDEDPLGPDNINWSQFIPELQ
• 3D-structure: PDB ID: 3G73; Classification: Transcription/dna; Method: X-ray diffraction; Resolution: 2.21 Å
• Function: Transcription factor regulating the expression of cell cycle genes essential for DNA replication and mitosis (PubMed:19160488, PubMed:20360045). Plays a role in the control of cell proliferation (PubMed:19160488). Also plays a role in DNA break repair, participating in the DNA damage checkpoint response (PubMed:17101782). Promotes transcription of PHB2 (PubMed:33754036). .
• Uniprot ID: FOXM1_HUMAN
• Ensembl ID: ENSG00000111206
• HGNC ID: HGNC:3818

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

Simvastatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Neuroblastoma [ICD-11: 2AOO.11] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Neuroblastoma [ICD-11: 2AOO.11]
• Resistant Drug: Simvastatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Terpenoid backbone biosynthesis; Activation; hsa00900
• In Vivo Model: NOD/SCID mice, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Like dipyridamole (41, 57), caffeine can block statin-induced feedback activation of SREBP2 and mevalonate pathway enzymes. Our data suggest that this action of caffeine depends on its activity as an antagonist of adenosine receptors (43, 59, 62), as evidenced by the findings that supplemental adenosine can abrogate the ability of caffeine to block statin-induced feedback activation SREBP2 and mevalonate pathway enzymes and to enhance the antigrowth effect of simvastatin.

References

• Ref 1: Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma. Cancer Res. 2023 Jul 5;83(13):2248-2261.