Molecule Information

General Information of the Molecule (ID: Mol00474)

• Name: Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) ,Homo sapiens
• Synonyms: G-protein coupled receptor 49; G-protein coupled receptor 67; G-protein coupled receptor HG38; GPR49; GPR67
• Molecule Type: Protein
• Gene Name: LGR5
• Gene ID: 8549
• Location: chr12:71439798-71586310[+]
• Sequence:
  MDTSRLGVLLSLPVLLQLATGGSSPRSGVLLRGCPTHCHCEPDGRMLLRVDCSDLGLSEL
  PSNLSVFTSYLDLSMNNISQLLPNPLPSLRFLEELRLAGNALTYIPKGAFTGLYSLKVLM
  LQNNQLRHVPTEALQNLRSLQSLRLDANHISYVPPSCFSGLHSLRHLWLDDNALTEIPVQ
  AFRSLSALQAMTLALNKIHHIPDYAFGNLSSLVVLHLHNNRIHSLGKKCFDGLHSLETLD
  LNYNNLDEFPTAIRTLSNLKELGFHSNNIRSIPEKAFVGNPSLITIHFYDNPIQFVGRSA
  FQHLPELRTLTLNGASQITEFPDLTGTANLESLTLTGAQISSLPQTVCNQLPNLQVLDLS
  YNLLEDLPSFSVCQKLQKIDLRHNEIYEIKVDTFQQLLSLRSLNLAWNKIAIIHPNAFST
  LPSLIKLDLSSNLLSSFPITGLHGLTHLKLTGNHALQSLISSENFPELKVIEMPYAYQCC
  AFGVCENAYKISNQWNKGDNSSMDDLHKKDAGMFQAQDERDLEDFLLDFEEDLKALHSVQ
  CSPSPGPFKPCEHLLDGWLIRIGVWTIAVLALTCNALVTSTVFRSPLYISPIKLLIGVIA
  AVNMLTGVSSAVLAGVDAFTFGSFARHGAWWENGVGCHVIGFLSIFASESSVFLLTLAAL
  ERGFSVKYSAKFETKAPFSSLKVIILLCALLALTMAAVPLLGGSKYGASPLCLPLPFGEP
  STMGYMVALILLNSLCFLMMTIAYTKLYCNLDKGDLENIWDCSMVKHIALLLFTNCILNC
  PVAFLSFSSLINLTFISPEVIKFILLVVVPLPACLNPLLYILFNPHFKEDLVSLRKQTYV
  WTRSKHPSLMSINSDDVEKQSCDSTQALVTFTSSSITYDLPPSSVPSPAYPVTESCHLSS
  VAFVPCL
• Function: Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development.
• Uniprot ID: LGR5_HUMAN
• Ensembl ID: ENSG00000139292
• HGNC ID: HGNC:4504

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) 3 drug(s) in total

Docetaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Docetaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpressed miR-340-5p inhibited cell proliferation and drug resistance with increased apoptosis of breast cancer cells through down-regulating LGR5 expression via Wnt/beta-catenin pathway.

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Colon cancer [2]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vivo Model: HT-29 xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: The miR-142-3p was markedly decreased in coloncancer specimens, in which it was negatively correlated withthe expression of CD133, Lgr5, and ABCG2. Transfection of miR-142-3p mimics in colon cancer cells downregulated cyclin D1expression, induced G1phase cell cycle arrest, and elevatedthe sensitivity of the cells to 5-fluorouracil. Furthermore,OCT4 suppressed miR-142-3p, and hypomethylation of theOCT4promoter was associated with a reduction in miR-142-3p.

Pyrvinium

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Anaplastic thyroid cancer [3]

• Sensitive Disease: Anaplastic thyroid cancer [ICD-11: 2D10.2]
• Sensitive Drug: Pyrvinium
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Wnt signaling pathway; Activation; hsa04310
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• Experiment for Molecule Alteration: Western blotting analysis; ART sensitivity assay
• Experiment for Drug Resistance: CCK-8 cell proliferation assay; Flow cytometry
• Mechanism Description: Pyrvinium pamoate can overcome artemisinin's resistance in anaplastic thyroid cancer. The resistance of CAL-62 to ART was related to the upregulation of the WNT signaling pathway.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Colon cancer [ICD-11: 2B90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Colon
• The Specified Disease: Colon cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.64E-105; Fold-change: 1.92E+00; Z-score: 3.36E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.91E-72; Fold-change: 2.42E+00; Z-score: 2.96E+00

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.02E-03; Fold-change: -2.90E-01; Z-score: -6.54E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 7.47E-05; Fold-change: -3.30E-02; Z-score: -1.45E-01

Thyroid cancer [ICD-11: 2D10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Thyroid
• The Specified Disease: Thyroid cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.08E-05; Fold-change: 7.66E-02; Z-score: 4.37E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.03E-02; Fold-change: 5.97E-03; Z-score: 2.82E-02

References

• Ref 1: LGR5 acts as a target of miR-340-5p in the suppression of cell progression and drug resistance in breast cancer via Wnt/Beta-catenin pathway. Gene. 2019 Jan 30;683:47-53. doi: 10.1016/j.gene.2018.10.014. Epub 2018 Oct 6.
• Ref 2: MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells. J Mol Med (Berl). 2013 Aug;91(8):989-1000. doi: 10.1007/s00109-013-1037-x. Epub 2013 Apr 26.
• Ref 3: Pyrvinium pamoate can overcome artemisinin's resistance in anaplastic thyroid cancer .BMC Complement Med Ther. 2021 May 28;21(1):156. doi: 10.1186/s12906-021-03332-z. 10.1186/s12906-021-03332-z