Molecule Information

General Information of the Molecule (ID: Mol00008)

• Name: Myeloma cell metalloproteinase (ADAM9) ,Homo sapiens
• Synonyms: ADAM 9; Cellular disintegrin-related protein; Meltrin-gamma; Metalloprotease/disintegrin/cysteine-rich protein 9; Myeloma cell metalloproteinase; KIAA0021; MCMP; MDC9; MLTNG
• Molecule Type: Protein
• Gene Name: ADAM9
• Gene ID: 8754
• Location: chr8:38996754-39105445[+]
• Sequence:
  MGSGARFPSGTLRVRWLLLLGLVGPVLGAARPGFQQTSHLSSYEIITPWRLTRERREAPR
  PYSKQVSYVIQAEGKEHIIHLERNKDLLPEDFVVYTYNKEGTLITDHPNIQNHCHYRGYV
  EGVHNSSIALSDCFGLRGLLHLENASYGIEPLQNSSHFEHIIYRMDDVYKEPLKCGVSNK
  DIEKETAKDEEEEPPSMTQLLRRRRAVLPQTRYVELFIVVDKERYDMMGRNQTAVREEMI
  LLANYLDSMYIMLNIRIVLVGLEIWTNGNLINIVGGAGDVLGNFVQWREKFLITRRRHDS
  AQLVLKKGFGGTAGMAFVGTVCSRSHAGGINVFGQITVETFASIVAHELGHNLGMNHDDG
  RDCSCGAKSCIMNSGASGSRNFSSCSAEDFEKLTLNKGGNCLLNIPKPDEAYSAPSCGNK
  LVDAGEECDCGTPKECELDPCCEGSTCKLKSFAECAYGDCCKDCRFLPGGTLCRGKTSEC
  DVPEYCNGSSQFCQPDVFIQNGYPCQNNKAYCYNGMCQYYDAQCQVIFGSKAKAAPKDCF
  IEVNSKGDRFGNCGFSGNEYKKCATGNALCGKLQCENVQEIPVFGIVPAIIQTPSRGTKC
  WGVDFQLGSDVPDPGMVNEGTKCGAGKICRNFQCVDASVLNYDCDVQKKCHGHGVCNSNK
  NCHCENGWAPPNCETKGYGGSVDSGPTYNEMNTALRDGLLVFFFLIVPLIVCAIFIFIKR
  DQLWRSYFRKKRSQTYESDGKNQANPSRQPGSVPRHVSPVTPPREVPIYANRFAVPTYAA
  KQPQQFPSRPPPPQPKVSSQGNLIPARPAPAPPLYSSLT
• Function: Cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5. May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins.
• Uniprot ID: ADAM9_HUMAN
• Ensembl ID: ENSG00000168615
• HGNC ID: HGNC:216

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

Dabrafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Melanoma [1]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Dabrafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: Sk-Mel28 cells; Skin; Homo sapiens (Human); CVCL_0526
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A.

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
• Cell Pathway Regulation: ADAM9/EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: HCT116-R cells; Colon; Homo sapiens (Human); CVCL_AU09
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay; Annexin V apoptosis assay
• Mechanism Description: miR20b suppresses cell proliferation and apoptosis and regulates cell cycle progression by targeting ADAM9 in HCT116-R cells, miR20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer.

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: 1.07E-01; Fold-change: 3.35E-02; Z-score: 4.11E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.47E-06; Fold-change: 7.13E-01; Z-score: 6.04E-01

Melanoma [ICD-11: 2C30]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Skin
• The Specified Disease: Melanoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.42E-01; Fold-change: 1.14E+00; Z-score: 6.94E-01

References

• Ref 1: miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A. J Exp Clin Cancer Res. 2019 Jun 21;38(1):272. doi: 10.1186/s13046-019-1238-4.
• Ref 2: miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer. Oncol Rep. 2017 Jan;37(1):123-130. doi: 10.3892/or.2016.5259. Epub 2016 Nov 18.