Molecule Information

General Information of the Molecule (ID: Mol04436)

• Name: Angiopoietin-related protein 4 (ANGPTL4) ,Homo sapiens
• Synonyms: Angiopoietin-like protein 4; Hepatic fibrinogen/angiopoietin-related protein
• Molecule Type: Protein
• Gene Name: ANGPTL4
• Gene ID: 51129
• Sequence:
  MSGAPTAGAALMLCAATAVLLSAQGGPVQSKSPRFASWDEMNVLAHGLLQLGQGLREHAE
  RTRSQLSALERRLSACGSACQGTEGSTDLPLAPESRVDPEVLHSLQTQLKAQNSRIQQL
  F HKVAQQQRHLEKQHLRIQHLQSQFGLLDHKHLDHEVAKPARRKRLPEMAQPVDPAHNV
  SR LHRLPRDCQELFQVGERQSGLFEIQPQGSPPFLVNCKMTSDGGWTVIQRRHDGSVDF
  NRP WEAYKAGFGDPHGEFWLGLEKVHSITGDRNSRLAVQLRDWDGNAELLQFSVHLGGE
  DTAY SLQLTAPVAGQLGATTVPPSGLSVPFSTWDQDHDLRRDKNCAKSLSGGWWFGTCS
  HSNLN GQYFRSIPQQRQKLKKGIFWKTWRGRYYPLQATTMLIQPMAAEAAS
• Function: Mediates inactivation of the lipoprotein lipase LPL, andthereby plays a role in the regulation of triglyceride clearance fromthe blood serum and in lipid metabolism . May also play arole in regulating glucose homeostasis and insulin sensitivity. Inhibits proliferation, migration, and tubule formation ofendothelial cells and reduces vascular leakage . Upon heterologous expression, inhibits the adhesionof endothelial cell to the extracellular matrix , and inhibits thereorganization of the actin cytoskeleton, formation of actin stressfibers and focal adhesions in endothelial cells that have adhered toANGPTL4-containing ECM . Depending oncontext, may modulate tumor-related angiogenesis .{ECO:0000250|UniProtKB:Q9Z1P8, ECO:0000269|PubMed:14583458,ECO:0000269|PubMed:17068295, ECO:0000269|PubMed:19270337,ECO:0000269|PubMed:21398697, ECO:0000269|PubMed:27929370,ECO:0000269|PubMed:29899144, ECO:0000305|PubMed:29899519}.; [ANGPTL4 N-terminal chain]: Mediates inactivation of thelipoprotein lipase LPL, and thereby plays an important role in theregulation of triglyceride clearance from the blood serum and in lipidmetabolism . Has higher activity in LPL inactivation than theuncleaved protein .{ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697,ECO:0000269|PubMed:27929370, ECO:0000269|PubMed:29899144}.
• Uniprot ID: ANGL4_HUMAN
• Ensembl ID: ENSG0000016777212
• HGNC ID: HGNC:16039

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

Quercetin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Quercetin
• Molecule Alteration: Expression; .
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Raf-MEK-ERK-PGC1alpha signaling pathway; Regulation; N.A.
• In Vitro Model: 22Rv-1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• In Vitro Model: PC-3 cells; Bone; Homo sapiens (Human); CVCL_0035
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vivo Model: BALB/c nude xenograft model; Mus musculus
• Experiment for Molecule Alteration: Metabolomics analysis; GST pull-down assay; Coimmunoprecipitation assay
• Experiment for Drug Resistance: Cellular thermal shift assay; Tumor xenografts assay
• Mechanism Description: The extracrine factor ANGPTL4 is primarily expressed in CAFs in PCa. When ANGPTL4 binds to IQ motif-containing GTPase-activating protein 1 (IQGAP1) on the PCa cell membrane, it activates the Raf-MEK-ERK-PGC1alpha axis, promoting mitochondrial biogenesis and OXPHOS metabolism, and thereby facilitating PCa growth and chemoresistance. Furthermore, virtual and functional screening strategies identified QGGP as a specific inhibitor of IQGAP1 that promotes its degradation. Combined with docetaxel treatment, QGGP can reverse the effects of CAFs and improve the responsiveness of PCa to chemotherapy.

References

• Ref 1: Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer. J Adv Res. 2024 Dec 6:S2090-1232(24)00559-9.