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Tumor suppressor p16 INK4a : Downregulation of galectin‐3, an endogenous competitor of the pro‐anoikis effector galectin‐1, in a pancreatic carcinoma model
Author(s) -
SanchezRuderisch Hugo,
Fischer Christian,
Detjen Katharina M.,
Welzel Martina,
Wimmel Anja,
Manning Joachim C.,
André Sabine,
Gabius HansJoachim
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07764.x
Subject(s) - anoikis , effector , galectin , biology , suppressor , microbiology and biotechnology , cancer research , downregulation and upregulation , endogeny , cell growth , cancer cell , cancer , biochemistry , genetics , gene
The tumor suppressor p16 INK4a 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 p16 INK4a ‐expressing pancreatic carcinoma cells (Capan‐1), lead to potent pro‐anoikis signals. We show that the p16 INK4a ‐dependent impact on growth‐regulatory lectins is not limited to galectin‐1, but also concerns galectin‐3. By monitoring its expression in relation to p16 INK4a 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 p16 INK4a 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 p16 INK4a 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.