Molecule Information

General Information of the Molecule (ID: Mol04342)

• Name: Insulin-like growth factor-binding protein 3 (IGFBP3) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: IGFBP3
• Gene ID: 3486
• Sequence:
  MQRARPTLWAAALTLLVLLRGPPVARAGASSAGLGPVVRCEPCDARALAQCAPPPAVCAE
  LVREPGCGCCLTCALSEGQPCGIYTERCGSGLRCQPSPDEARPLQALLDGRGLCVNASA
  V SRLRAYLLPAPPAPGNASESEEDRSAGSVESPSVSSTHRVSDPKFHPLHSKIIIIKKG
  HA KDSQRYKVDYESQSTDTQNFSSESKRETEYGPCRREMEDTLNHLKFLNVLSPRGVHI
  PNC DKKGFYKKKQCRPSKGRKRGFCWCVDKYGQPLPGYTTKGKEDVHCYSMQSK
• Function: Multifunctional protein that plays a critical role inregulating the availability of IGFs such as IGF1 and IGF2 to theirreceptors and thereby regulates IGF-mediated cellular processesincluding proliferation, differentiation, and apoptosis in a cell-typespecific manner . Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by itsreceptor TMEM219/IGFBP-3R . Inhibits the positiveeffect of humanin on insulin sensitivity . Promotestesticular germ cell apoptosis . Acts via LRP-1/alpha2M receptor, also known as TGF-beta type V receptor, to mediatecell growth inhibition independent of IGF1 .Mechanistically, induces serine-specific dephosphorylation of IRS1 orIRS2 upon ligation to its receptor, leading to the inhibitory cascade. In the nucleus, interacts with transcription factorssuch as retinoid X receptor-alpha/RXRA to regulate transcriptionalsignaling and apoptosis .{ECO:0000269|PubMed:10874028, ECO:0000269|PubMed:15371331,ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19556345,ECO:0000269|PubMed:19623253, ECO:0000269|PubMed:19952275,ECO:0000269|PubMed:20353938}.
• Uniprot ID: IBP3_HUMAN
• Ensembl ID: ENSG0000014667416
• HGNC ID: HGNC:5472

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

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

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

Fulvestrant

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 FulR cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Immunoblotting assay; qPCR
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Elevated expression of IGFBP-3 is associated with fulvestrant resistance in MCF-7 cells. MCF-7FulR cells expressed significantly higher levels of IGFBP-3 transcript and protein compared to parental cells.

References

• Ref 1: Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells. Front Oncol. 2024 Nov 15;14:1452981.