Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway.


Journal Article

Activation of tumor suppressors for the treatment of human cancer has been a long sought, yet elusive, strategy. PTEN is a critical tumor suppressive phosphatase that is active in its dimer configuration at the plasma membrane. Polyubiquitination by the ubiquitin E3 ligase WWP1 (WW domain-containing ubiquitin E3 ligase 1) suppressed the dimerization, membrane recruitment, and function of PTEN. Either genetic ablation or pharmacological inhibition of WWP1 triggered PTEN reactivation and unleashed tumor suppressive activity. WWP1 appears to be a direct MYC (MYC proto-oncogene) target gene and was critical for MYC-driven tumorigenesis. We identified indole-3-carbinol, a compound found in cruciferous vegetables, as a natural and potent WWP1 inhibitor. Thus, our findings unravel a potential therapeutic strategy for cancer prevention and treatment through PTEN reactivation.

Full Text

Duke Authors

Cited Authors

  • Lee, Y-R; Chen, M; Lee, JD; Zhang, J; Lin, S-Y; Fu, T-M; Chen, H; Ishikawa, T; Chiang, S-Y; Katon, J; Zhang, Y; Shulga, YV; Bester, AC; Fung, J; Monteleone, E; Wan, L; Shen, C; Hsu, C-H; Papa, A; Clohessy, JG; Teruya-Feldstein, J; Jain, S; Wu, H; Matesic, L; Chen, R-H; Wei, W; Pandolfi, PP

Published Date

  • May 17, 2019

Published In

Volume / Issue

  • 364 / 6441

PubMed ID

  • 31097636

Pubmed Central ID

  • 31097636

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aau0159


  • eng

Conference Location

  • United States