| Autor: |
Katharina Detjen, Sabine André, Christian Fischer, Anja Wimmel, Hugo Sanchez-Ruderisch, M. Welzel, Hans-Joachim Gabius, Joachim C. Manning |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
FEBS Journal. 277:3552-3563 |
| ISSN: |
1742-464X |
| DOI: |
10.1111/j.1742-4658.2010.07764.x |
| Popis: |
The tumor suppressor p16INK4a has functions beyond cell-cycle control via cyclin-dependent kinases. A coordinated remodeling of N- and O-glycosylation, and an increase in the presentation of the endogenous lectin galectin-1 sensing these changes on the surface of p16INK4a-expressing pancreatic carcinoma cells (Capan-1), lead to potent pro-anoikis signals. We show that the p16INK4a-dependent impact on growth-regulatory lectins is not limited to galectin-1, but also concerns galectin-3. By monitoring its expression in relation to p16INK4a status, as well as running anoikis assays with galectin-3 and cell transfectants with up- or downregulated lectin expression, a negative correlation between anoikis and the presence of this lectin was established. Nuclear run-off and northern blotting experiments revealed an effect of the presence of p16INK4a on steady-state levels of galectin-3-specific mRNA that differed from decreasing the transcriptional rate. On the cell surface, galectin-3 interferes with galectin-1, which initiates signaling toward its pro-anoikis activity via caspase-8 activation. The detected opposite effects of p16INK4a at the levels of growth-regulatory galectins-1 and -3 shift the status markedly towards the galectin-1-dependent pro-anoikis activity. A previously undescribed orchestrated fine-tuning of this effector system by a tumor suppressor is discovered. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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