Title | The Par-4/PTEN connection in tumor suppression. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Diaz-Meco MT, Abu-Baker S |
Journal | Cell Cycle |
Volume | 8 |
Issue | 16 |
Pagination | 2518-22 |
Date Published | 2009 Aug 15 |
ISSN | 1551-4005 |
Keywords | Animals, Humans, Male, Mice, Models, Biological, Prostatic Neoplasms, PTEN Phosphohydrolase, Receptors, Thrombin, Signal Transduction |
Abstract | Tumor suppressors function in a coordinated regulatory network, and their inactivation is a key step in carcinogenesis. The tumor suppressor Par-4 is a novel integral player in the PTEN network. Thus, Par-4 is absent in a high percentage of human prostate carcinomas, and its loss is concomitantly associated with PTEN loss. Genetic ablation of Par-4 induces fully invasive prostate carcinomas in PTEN-heterozygous mice. In contrast, Par-4 deficiency alone, like PTEN heterozygosis, results in lesions that are unable to progress beyond the benign neoplastic stage known as PIN. At this PIN transition, the mutual induction of Par-4 and PTEN is an additional regulatory step in preventing cancer progression. Par-4 deficiency cooperates with PTEN haploinsufficiency in prostate cancer initiation and progression and their simultaneous inactivation, in addition to enhancing Akt activation, sets in motion a unique mechanism involving the synergistic activation of NFkappaB. These results suggest that the concurrent interruption of complementary signaling pathways targeting PI3K/Akt and NFkappaB activation could provide new and effective strategies for cancer therapy. |
DOI | 10.4161/cc.8.16.9384 |
Alternate Journal | Cell Cycle |
PubMed ID | 19625770 |
Grant List | 1R01CA134530 / CA / NCI NIH HHS / United States |
Related Faculty:
Maria Diaz-Meco Conde, Ph.D.