TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000284274
  • Gene Name:OTULIN
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:Wnt/β-catenin
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:breast cancer
  • Tissue:Human breast cancercell lines MDA-MB-231, MDA-MB-468, MCF7, and LM2

Other information

  • Title:ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to enhance drug resistance in breast cancers
  • Journal:NATURE COMMUNICATIONS
  • Published:2020
  • PubMed ID:32770022
  • Abstract:Dysregulated Wnt/β-catenin activation plays a critical role in cancer progression, metastasis, and drug resistance. Genotoxic agents such as radiation and chemotherapeutics have been shown to activate the Wnt/β-catenin signaling although the underlying mechanism remains incompletely understood. Here, we show that genotoxic agent-activated Wnt/β-catenin signaling is independent of the FZD/LRP heterodimeric receptors and Wnt ligands. OTULIN, a linear linkage-specific deubiquitinase, is essential for the DNA damage-induced β-catenin activation. OTULIN inhibits linear ubiquitination of β-catenin, which attenuates its Lys48-linked ubiquitination and proteasomal degradation upon DNA damage. The association with β-catenin is enhanced by OTULIN Tyr56 phosphorylation, which depends on genotoxic stress-activated ABL1/c-Abl. Inhibiting OTULIN or Wnt/β-catenin sensitizes triple-negative breast cancer xenograft tumors to chemotherapeutics and reduces metastasis. Increased OTULIN levels are associated with aggressive molecular subtypes and poor survival in breast cancer patients. Thus, OTULIN-mediated Wnt/β-catenin activation upon genotoxic treatments promotes drug resistance and metastasis in breast cancers.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3