Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy

Int J Med Sci. 2020 Apr 6;17(8):995-1005. doi: 10.7150/ijms.42805. eCollection 2020.


The inhibitor of DNA binding (Id) proteins are regulators of cell cycle and cell differentiation. Of all Id family proteins, Id1 is mostly linked to tumorigenesis, cellular senescence as well as cell proliferation and survival. Id1 is a stem cell-like gene more than a classical oncogene. Id1 is overexpressed in numerous types of cancers and exerts its promotion effect to these tumors through different pathways. Briefly, Id1 was found significantly correlated with EMT-related proteins, K-Ras signaling, EGFR signaling, BMP signaling, PI3K/Akt signaling, WNT and SHH signaling, c-Myc signaling, STAT3 signaling, RK1/2 MAPK/Egr1 pathway and TGF-β pathway, etc. Id1 has potent effect on facilitating tumorous angiogenesis and metastasis. Moreover, high expression of Id1 plays a facilitating role in the development of drug resistance, including chemoresistance, radiation resistance and resistance to drugs targeting angiogenesis. However, controversial results were also obtained. Overall, Id1 represent a promising target of anti-tumor therapeutics based on its potent promotion effect to cancer. Numerous drugs were found exerting their anti-tumor function through Id1-related signaling pathways, such as fucoidan, berberine, tetramethylpyrazine, crizotinib, cannabidiol and vinblastine.

Keywords: Angiogenesis; Cancer; Id1; Resistance; Signaling pathway; Target.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis / drug effects
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cellular Senescence / drug effects
  • Disease Models, Animal
  • Drug Resistance, Neoplasm / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Differentiation Protein 1 / antagonists & inhibitors
  • Inhibitor of Differentiation Protein 1 / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / pathology*


  • Antineoplastic Agents
  • Inhibitor of Differentiation Protein 1