Molecule Information

General Information of the Molecule (ID: Mol04061)

• Name: Podoplanin (PDPN) ,Homo sapiens
• Synonyms: Aggrus; Glycoprotein 36; PA2.26 antigen; T1-alpha
• Molecule Type: Protein
• Gene Name: PDPN
• Gene ID: 10630
• Location: chr1:13583465-13617957[+]
• Sequence:
  MWKVSALLFVLGSASLWVLAEGASTGQPEDDTETTGLEGGVAMPGAEDDVVTPGTSEDRY
  KSGLTTLVATSVNSVTGIRIEDLPTSESTVHAQEQSPSATASNVATSHSTEKVDGDTQTT
  VEKDGLSTVTLVGIIVGVLLAIGFIGAIIVVVMRKMSGRYSP
• 3D-structure: PDB ID: 7CQD; Classification: Hydrolase/immune system; Method: X-ray diffraction; Resolution: 3.20 Å
• Function: Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activation in platelets and leading to platelet activation and/or aggregation (PubMed:14522983, PubMed:15231832, PubMed:17222411, PubMed:17616532, PubMed:18215137). Interaction with CD9, on the contrary, attenuates platelet aggregation induced by PDPN (PubMed:18541721). Through MSN or EZR interaction promotes epithelial- mesenchymal transition (EMT) leading to ERZ phosphorylation and triggering RHOA activation leading to cell migration increase and invasiveness (PubMed:17046996, PubMed:21376833). Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (PubMed:20962267). In lymph nodes (LNs), controls fibroblastic reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction of the actomyosin by maintaining ERM proteins (EZR; MSN and RDX) and MYL9 activation through association with unknown transmembrane proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 activation (By similarity). Through binding with LGALS8 may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix (PubMed:19268462). In keratinocytes, induces changes in cell morphology showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion (PubMed:15515019). Controls invadopodia stability and maturation leading to efficient degradation of the extracellular matrix (ECM) in tumor cells through modulation of RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivation of CFL1 (PubMed:25486435). Required for normal lung cell proliferation and alveolus formation at birth (By similarity). Does not function as a water channel or as a regulator of aquaporin-type water channels (PubMed:9651190). Does not have any effect on folic acid or amino acid transport (By similarity). .
• Uniprot ID: PDPN_HUMAN
• Ensembl ID: ENSG00000162493
• HGNC ID: HGNC:29602

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

Enzalutamide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

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

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Enzalutamide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: C4-2B cells; Prostate; Homo sapiens (Human); CVCL_4784
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: We compared the transcriptomic profile of paired enzalutamide-sensitive and resistant LNCaP and C4-18B prostate cancer cells for identification of genes involved in drug resistance by performing an unbiased bioinformatics analysis and further validation

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

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Enzalutamide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: We compared the transcriptomic profile of paired enzalutamide-sensitive and resistant LNCaP and C4-9B prostate cancer cells for identification of genes involved in drug resistance by performing an unbiased bioinformatics analysis and further validation

References

• Ref 1: Metabolic Reprogramming and Predominance of Solute Carrier Genes during Acquired Enzalutamide Resistance in Prostate Cancer. Cells. 2020 Nov 24;9(12):2535.