Molecule Information

General Information of the Molecule (ID: Mol04128)

• Name: Metastasis associated in colon cancer protein 1 (MACC1) ,Homo sapiens
• Synonyms: SH3 domain-containing protein 7a5
• Molecule Type: Protein
• Gene Name: MACC1
• Gene ID: 346389
• Location: chr7:20134655-20217404[-]
• Sequence:
  MLITERKHFRSGRIAQSMSEANLIDMEAGKLSKSCNITECQDPDLLHNWPDAFTLRGNNA
  SKVANPFWNQLSASNPFLDDITQLRNNRKRNNISILKEDPFLFCREIENGNSFDSSGDEL
  DVHQLLRQTSSRNSGRSKSVSELLDILDDTAHAHQSIHNSDQILLHDLEWLKNDREAYKM
  AWLSQRQLARSCLDLNTISQSPGWAQTQLAEVTIACKVNHQGGSVQLPESDITVHVPQGH
  VAVGEFQEVSLRAFLDPPHMLNHDLSCTVSPLLEIMLGNLNTMEALLLEMKIGAEVRKDP
  FSQVMTEMVCLHSLGKEGPFKVLSNCYIYKDTIQVKLIDLSQVMYLVVAAQAKALPSPAA
  TIWDYIHKTTSIGIYGPKYIHPSFTVVLTVCGHNYMPGQLTISDIKKGGKNISPVVFQLW
  GKQSFLLDKPQDLSISIFSCDPDFEVKTEGERKEIKQKQLEAGEVVHQQFLFSLVEHREM
  HLFDFCVQVEPPNGEPVAQFSITTPDPTPNLKRLSNLPGYLQKKEEIKSAPLSPKILVKY
  PTFQDKTLNFSNYGVTLKAVLRQSKIDYFLEYFKGDTIALLGEGKVKAIGQSKVKEWYVG
  VLRGKIGLVHCKNVKVISKEQVMFMSDSVFTTRNLLEQIVLPLKKLTYIYSVVLTLVSEK
  VYDWKVLADVLGYSHLSLEDFDQIQADKESEKVSYVIKKLKEDCHTERNTRKFLYELIVA
  LLKMDCQELVARLIQEAAVLTSAVKLGKGWRELAEKLVRLTKQQMEAYEIPHRGNTGDVA
  VEMMWKPAYDFLYTWSAHYGNNYRDVLQDLQSALDRMKNPVTKHWRELTGVLILVNSLEV
  LRVTAFSTSEEV
• Function: Acts as a transcription activator for MET and as a key regulator of HGF-MET signaling. Promotes cell motility, proliferation and hepatocyte growth factor (HGF)-dependent scattering in vitro and tumor growth and metastasis in vivo. .
• Uniprot ID: MACC1_HUMAN
• Ensembl ID: ENSG00000183742
• HGNC ID: HGNC:30215

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

Trastuzumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: HER2-positive advanced gastric cancer [ICD-11: 2B72.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: HER2-positive advanced gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Human papillomavirus infection; Activation; hsa05165
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: NCI-N87 with high HER2 expressions cells; Stomach; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vitro Model: MKN45 parental cells with high HER2 expressions; Stomach; Homo sapiens (Human); CVCL_0434
• In Vitro Model: SGC-7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects.

Disease Class: HER2-positive advanced gastric cancer [ICD-11: 2B72.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: HER2-positive advanced gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Human papillomavirus infection; Activation; hsa05165
• In Vivo Model: BALB/c nude mouse xenograft model using NCI-N87 MACC1-overexpressing; Mice
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: HER2-positive advanced gastric cancer [ICD-11: 2B72.1] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: HER2-positive advanced gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Trastuzumab
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Human papillomavirus infection; Activation; hsa05165
• In Vitro Model: MKN45 cells; Liver; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects.

Disease Class: HER2-positive advanced gastric cancer [ICD-11: 2B72.1] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: HER2-positive advanced gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Human papillomavirus infection; Activation; hsa05165
• In Vivo Model: BALB/c nude mouse xenograft model using NCI-N87 MACC1-silenced; Mice
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects.

References

• Ref 1: A new mechanism of trastuzumab resistance in gastric cancer: MACC1 promotes the Warburg effect via activation of the PI3K/AKT signaling pathway. J Hematol Oncol. 2016 Aug 31;9(1):76.