Molecule Information

General Information of the Molecule (ID: Mol00542)

• Name: Osteopontin (OPN) ,Homo sapiens
• Synonyms: Bone sialoprotein 1; Nephropontin; Secreted phosphoprotein 1; SPP-1; Urinary stone protein; Uropontin; BNSP; OPN; PSEC0156
• Molecule Type: Protein
• Gene Name: SPP1
• Gene ID: 6696
• Location: chr4:87975667-87983532[+]
• Sequence:
  MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQNA
  VSSEETNDFKQETLPSKSNESHDHMDDMDDEDDDDHVDSQDSIDSNDSDDVDDTDDSHQS
  DESHHSDESDELVTDFPTDLPATEVFTPVVPTVDTYDGRGDSVVYGLRSKSKKFRRPDIQ
  YPDATDEDITSHMESEELNGAYKAIPVAQDLNAPSDWDSRGKDSYETSQLDDQSAETHSH
  KQSRLYKRKANDESNEHSDVIDSQELSKVSREFHSHEFHSHEDMLVVDPKSKEEDKHLKF
  RISHELDSASSEVN
• 3D-structure: PDB ID: 3CXD; Classification: Immune system; Method: X-ray diffraction; Resolution: 2.80 Å
• Function: Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction.
• Uniprot ID: OSTP_HUMAN
• Ensembl ID: ENSG00000118785
• HGNC ID: HGNC:11255

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) 2 drug(s) in total

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [ICD-11: 2C60.3] [1]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Doxorubicin
• 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 invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: p53 signaling pathway; Activation; hsa04115
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The microRNA miR-181c enhances chemosensitivity and reduces chemoresistance in breast cancer cells via down-regulating osteopontin.

Irinotecan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Colon cancer [ICD-11: 2B90.1] [2]

• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Resistant Drug: Irinotecan
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NF+kB signaling pathway; Activation; hsa04218
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: SW-480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• Experiment for Molecule Alteration: Immunoblotting assay; qRT-PCR; Immunofluorescence staining assay; Reporter Gene assay; RNA sequencing assay
• Experiment for Drug Resistance: Cell cytotoxicity assay; Tumorigenicity assay
• Mechanism Description: Our data suggest that irinotecan upregulates various oncogenes, proliferative pathways, and metastatic markers, which may compromise its efficacy. SN38 induces p53-independent CDKIs and regulates cancer cell growth. OPN silencing regulates the SN38-mediated increase in PD-L1. Inhibition of non-canonical NF-kappaB signaling by QNZ results in the regulation of SN38-induced survivin and ISG15 (Figure 7). The targeting of OPN, PD-L1, ISG15, and NF-kappaB pathways may elevate irinotecan potency and lead to its combination with immunomodulatory therapies for CRC prognostic strategies.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

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: 4.99E-100; Fold-change: 1.67E+00; Z-score: 2.03E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.23E-10; Fold-change: 1.03E+00; Z-score: 1.18E+00

References

• Ref 1: The microRNA miR-181c enhances chemosensitivity and reduces chemoresistance in breast cancer cells via down-regulating osteopontin. Int J Biol Macromol. 2019 Mar 15;125:544-556. doi: 10.1016/j.ijbiomac.2018.12.075. Epub 2018 Dec 8.
• Ref 2: Overcoming Irinotecan Resistance by Targeting Its Downstream Signaling Pathways in Colon Cancer. Cancers (Basel). 2024 Oct 15;16(20):3491.