Journal
NATURE CELL BIOLOGY
Volume 11, Issue 6, Pages 694-U22Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1875
Keywords
-
Categories
Funding
- National Science Council
- Department of Health, Executive Yuan of the Republic of China, through the National Research Program for Genomic Medicine [DOH94-TD-G-111-020, DOH95-TD-G-111-010, DOH96-TD-G-111-009, DOH97-TD-G-111-018, DOH98-TD-G-111-007, NSC97-3112-B-002-033, NSC97-2314-B-002-146-MY3]
Ask authors/readers for more resources
The tumour suppressor p53 is known to prevent cancer progression by inhibiting proliferation and inducing apoptosis of tumour cells. Slug, an invasion promoter, exerts its effects by repressing E-cadherin transcription. Here we show that wild-type p53 (wtp53) suppresses cancer invasion by inducing Slug degradation, whereas mutant p53 may stabilize Slug protein. In non-small-cell lung cancer (NSCLC), mutation of p53 correlates with low MDM2, high Slug and low E-cadherin expression. This expression profile is associated with poor overall survival and short metastasis-free survival in patients with NSCLC. wtp53 upregulates MDM2 and forms a wtp53-MDM2-Slug complex that facilitates MDM2-mediated Slug degradation. Downregulation of Slug by wtp53 or MDM2 enhances E-cadherin expression and represses cancer cell invasiveness. In contrast, mutant p53 inactivates Slug degradation and leads to Slug accumulation and increased cancer cell invasiveness. Our findings indicate that wtp53 and p53 mutants may differentially control cancer invasion and metastasis through the p53-MDM2-Slug pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available