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Reactivation of PTEN Tumor Suppressor for Cancer Treatment Through Inhibition of a MYC-WWP1 Inhibitory Pathway

Reactivation of PTEN Tumor Suppressor for Cancer Treatment Through Inhibition of a MYC-WWP1 Inhibitory Pathway

Yu-Ru Lee, Ming Chen, Jonathan D Lee, Jinfang Zhang, Shu-Yu Lin, Tian-Min Fu, Hao Chen, Tomoki Ishikawa, Shang-Yin Chiang, Jesse Katon, Yang Zhang, Yulia V Shulga, Assaf C Bester, Jacqueline Fung, Emanuele Monteleone, etc.

Science. 2019 May 17;364(6441):eaau0159.

PMID: 31097636

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415043	WWP1 Active human			Price

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