Back to Search
Start Over
Inhibition of Tcf-4 Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer Cells.
- Source :
-
PLoS ONE . Sep2012, Vol. 7 Issue 9, Special section p1-9. 9p. - Publication Year :
- 2012
-
Abstract
- Aberrant activation of β-catenin/Tcf-4 signaling has been implicated in human carcinogenesis, including colorectal cancer. In this study, we compared the effects of Tcf-4 knockdown with β-catenin knockdown on cell proliferation, apoptosis, and chemosensitivity in SW480 and HCT116 colon cancer cells using adenoviral vector-mediated short hairpin RNA (shRNA). Our results show that, compared to β-catenin knockdown, Tcf-4 knockdown more effectively inhibited colony formation, induced apoptosis, and increased 5-FU and oxaliplatin-mediated cytotoxicity in colon cancer cells. We further investigated the mechanisms involved in the different efficacies observed with β-catenin and Tcf-4 knockdown in colon cancer cells. FOXO4 is a member of the subfamily of mammalian FOXO forkhead transcription factors and plays a major role in controlling cellular proliferation, apoptosis, and DNA repair. Our data showed that the protein level of FOXO4 did not change after treatment with both β-catenin and Tcf-4 shRNA. However, β-catenin shRNA was found to increase the accumulation of phosphorylated FOXO4 S193 and decrease the expression of FOXO target genes p27Kip1 and MnSOD, whereas Tcf-4 shRNA showed the opposite effect. Therefore, compared to β-catenin knockdown, Tcf-4 knockdown shows better efficacy for inhibiting proliferation and inducing apoptosis of colorectal cancer cells, which may be related to increased FOXO4 transcriptional activity. These results suggest that Tcf-4 is an attractive potential therapeutic target for colorectal cancer therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 82447410
- Full Text :
- https://doi.org/10.1371/journal.pone.0045617