Targeting the β-catenin/TCF transcriptional complex in the treatment of multiple myeloma
摘要：
Multiple myeloma (MM) is an invariably fatal form of cancer characterized by clonal proliferation of malignant plasma cells in the bone marrow. The canonical Wnt signaling pathway is activated in MM cells through constitutively active β-catenin, a messenger molecule relevant to growth, survival, and migration of MM cells. The identification of a number of small molecular compounds, such as PKF115-584, which disrupt the interaction of the transcriptionally active β-catenin/TCF protein complex, provides valuable new therapeutic tools to target an alternative pathway in MM independent of the proteasome. Here we evaluated the transcriptional, proteomic, signaling changes, and biological sequelae associated with the inhibition of Wnt signaling in MM by PKF115-584. The compound blocks expression of Wnt target genes and induces cytotoxicity in both patient MM cells and MM cell lines without a significant effect in normal plasma cells. In xenograft models of human MM, PKF115-584 inhibits tumor growth and prolongs survival. Taken together, these data demonstrate the efficacy of disrupting the β-catenin/TCF transcriptional complex to exploit tumor dependence on Wnt signaling as a therapeutic approach in the treatment of MM.
展开
DOI：
10.1073/pnas.0610299104
被引量：
年份：
2007
Taylor & Francis
国家科技图书文献中心
(权威机构)
万方医学
掌桥科研
Semantic Scholar
查看更多
dx.doi.org
NCBI
NCBI
(全网免费下载)
Europe PMC
(全网免费下载)
NCBI
Europe PMC
JSTOR
AACR
adsabs.harvard.edu
AGRIS
ResearchGate
(全网免费下载)
ResearchGate
EBSCO
iv.iiarjournals.org
pubag.nal.usda.gov
bloodjournal.org
pnas.org
pubfacts.com
The National Academy of Sciences of the United States of America
(全网免费下载)
onAcademic
jimmunol.org
deepdyve.com
mendeley.com
frontiersin.org
bvsalud.org
asheducationbook.hematologylibrary.org
pnas.org
(全网免费下载)
haematologica.org
Europe PMC
(全网免费下载)
NCBI
(全网免费下载)
ResearchGate
(全网免费下载)
The National Academy of Sciences of the United States of America
(全网免费下载)
pnas.org
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
研究点推荐
引用走势
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
