Authors
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, Lixin Wan, Chen Shen, Chih-Hung Hsu, Antonella Papa, John G Clohessy, Julie Teruya-Feldstein, Suresh Jain, Hao Wu, Lydia Matesic, Ruey-Hwa Chen, Wenyi Wei, Pier Paolo Pandolfi
Publication date
2019/5/17
Journal
Science
Volume
364
Issue
6441
Publisher
American Association for the Advancement of Science
Description
INTRODUCTION
Inhibition of oncogenic proteins represents a mainstay approach for cancer therapeutic development. By contrast, pharmacological modulation of tumor suppressor activity for the treatment of cancer has remained elusive. PTEN is a potent tumor suppressor gene, antagonizing the proto-oncogenic phosphoinositide 3-kinase (PI3K)–AKT signaling pathway and governing fundamental cellular processes. Cancer cells cannot afford to lose complete PTEN activity prematurely, because this would trigger cellular senescence, making PTEN an “obligate haploinsufficient” tumor suppressor gene. For this reason, PTEN is frequently dysregulated through monoallelic loss, aberrant subcellular localization, and/or posttranslational modification in human cancers as well as in cancer susceptibility syndromes such as PTEN hamartoma tumor syndrome (PHTS). Because PTEN overexpression in mice results in a …
Scholar articles
YR Lee, M Chen, JD Lee, J Zhang, SY Lin, TM Fu… - Science, 2019