Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 287, Issue 43, Pages 36435-36442Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.397125
Keywords
-
Categories
Funding
- American Cancer Society
- American Association for Cancer Research
- Department of Defense Breast Cancer Research Program
- Schweppe Foundation
- Lynn Sage Foundation
- National Institutes of Health Carcinogenesis Training Grant [T32-CA009560-21]
- Malkin Scholar Award from the Robert H. Lurie Comprehensive Cancer Center
Ask authors/readers for more resources
Epithelial-mesenchymal transition (EMT), a tightly regulated process that is critical for development, is frequently re-activated during cancer metastasis and recurrence. We reported previously that CD44 isoform switching is critical for EMT and showed that the splicing factor ESRP1 inhibits CD44 isoform switching during EMT. However, the mechanism by which ESRP1 is regulated during EMT has not been fully understood. Here we show that the transcription repressor Snail binds to E-boxes in the ESRP1 promoter, causing repression of the ESRP1 gene. Biochemically, we define the mechanism by which ESRP1 regulates CD44 alternative splicing: ESRP1 binds to the intronic region flanking a CD44 variable exon and causes increased variable exon inclusion. We further show that ectopically expressing ESRP1 inhibits Snail-induced EMT, suggesting that down-regulation of ESRP1 is required for function by Snail in EMT. Together, these data reveal how the transcription factor Snail mediates EMT through regulation of a splicing factor.
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