Molecule Information

General Information of the Molecule (ID: Mol00123)

• Name: Mucin-1 (MUC1) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: MUC1
• Gene ID: 4582
• Location: chr1:155185824-155192916[-]
• Sequence:
  MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSVPSSTEKNAVSMTSSV
  LSSHSPGSGSSTTQGQDVTLAPATEPASGSAATWGQDVTSVPVTRPALGSTTPPAHDVTS
  APDNKPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDNRPALGSTAPPVHNVTS
  ASGSASGSASTLVHNGTSARATTTPASKSTPFSIPSHHSDTPTTLASHSTKTDASSTHHS
  SVPPLTSSNHSTSPQLSTGVSFFFLSFHISNLQFNSSLEDPSTDYYQELQRDISEMFLQI
  YKQGGFLGLSNIKFRPGSVVVQLTLAFREGTINVHDVETQFNQYKTEAASRYNLTISDVS
  VSDVPFPFSAQSGAGVPGWGIALLVLVCVLVALAIVYLIALAVCQCRRKNYGQLDIFPAR
  DTYHPMSEYPTYHTHGRYVPPSSTDRSPYEKVSAGNGGSSLSYTNPAVAATSANL
• Function: The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.; FUNCTION: The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.
• Uniprot ID: MUC1_HUMAN
• Ensembl ID: ENSG00000185499
• HGNC ID: HGNC:7508

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

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung cancer [1]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: Rapamycin signaling pathway; Inhibition; hsa04211
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase activity assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR128 can effectively suppress PTX-resistant lung cancer stem cells via inhibition of BMI-1 and MUC1-C, thus downregulating the PI3k/AkT pathway and the rapamycin pathway.

Tamoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: MUC1, an oncoprotein, upregulates the expression of various enzymes involved in cholesterol metabolism. The overexpression of MUC1 has been found to be correlated with TAM resistance and poor survival. Cholesteryl esters of oleic and stearic acids are responsible for the proliferation and invasiveness of tumors. MUC1 upregulates the expression of the ACAT enzyme, therefore inhibition of cancer cell growth by TAM is minimized leading to resistance against it.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.28E-51; Fold-change: -7.25E-01; Z-score: -1.38E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.41E-10; Fold-change: -3.93E-01; Z-score: -4.09E-01

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: 1.85E-53; Fold-change: 1.61E+00; Z-score: 1.37E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.93E-08; Fold-change: 1.90E+00; Z-score: 1.19E+00

References

• Ref 1: MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells. Oncotarget. 2017 Nov 30;8(66):110540-110551. doi: 10.18632/oncotarget.22818. eCollection 2017 Dec 15.
• Ref 2: Metabolic reprograming confers tamoxifen resistance in breast cancer. Chem Biol Interact. 2021 Sep 25;347:109602. doi: 10.1016/j.cbi.2021.109602. Epub 2021 Jul 28.