Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway
Academic Article
Publication Date:
2019
Short description:
Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway / Lee, Y.-R., Chen, M., Lee, J.D., Zhang, J., Lin, S.-Y., Fu, T.-M., Chen, H., Ishikawa, T., Chiang, S.-Y., Katon, J., Zhang, Y., Shulga, Y.V., Bester, A.C., Fung, J., Monteleone, E., Wan, L., Shen, C., Hsu, C.-H., Papa, A., Clohessy, J.G., et al.. - In: SCIENCE. - ISSN 0036-8075. - 364:6441(2019), pp. 1-17. [10.1126/science.aau0159]
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.
Iris type:
1.1 Articolo in rivista
Keywords:
Anticarcinogenic Agents; Carcinogenesis; HEK293 Cells; Humans; Indoles; Male; Neoplasms; PTEN Phosphohydrolase; Protein Multimerization; Proto-Oncogene Proteins c-myc; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Ubiquitination
List of contributors:
Lee, Y. -R.; Chen, M.; Lee, J. D.; Zhang, J.; Lin, S. -Y.; Fu, T. -M.; Chen, H.; Ishikawa, T.; Chiang, S. -Y.; Katon, J.; Zhang, Y.; Shulga, Y. V.; Bester, A. C.; Fung, J.; Monteleone, E.; Wan, L.; Shen, C.; Hsu, C. -H.; Papa, A.; Clohessy, J. G.; Teruya-Feldstein, J.; Jain, S.; Wu, H.; Matesic, L.; Chen, R. -H.; Wei, W.; Pandolfi, P. P.
Published in: