Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 231, Issue 9, Pages 1932-1940Publisher
WILEY-BLACKWELL
DOI: 10.1002/jcp.25293
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science [25253095, 25461602]
- Grants-in-Aid for Scientific Research [25461602] Funding Source: KAKEN
Ask authors/readers for more resources
Malignant rhabdoid tumor (MRT) is a rare aggressive pediatric cancer characterized by inactivation of SNF5, a core subunit of SWI/SNF complexes. Previously, we showed that SNF5 contributes to transcriptional activation of NOXA, a pro-apoptotic protein that binds and inhibits the anti-apoptotic protein MCL-1. In this study, we found that NOXA expression was downregulated in MRT cell lines as well as in clinical MRT samples and that ectopically expressed NOXA bound MCL-1 and increased the sensitivity of MRT cell lines to doxorubicin (DOX) by promoting apoptosis. Consistent with this finding, knockdown of MCL-1 in MRT cell lines induced apoptosis and increased DOX sensitivity in MRT cells, and the MCL-1 inhibitor TW-37 synergized with DOX to induce MRT cell death. Our results suggest that modulation of the NOXA/MCL-1 pathway may be a potential strategy for the treatment of patients with MRT. (C) 2015 Wiley Periodicals, Inc.
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