Wnt activity defines colon cancer stem cells and is regulated by the microenvironment (Nat Cell Biol, 2010, 12:468-476)

報告日期: 2010/10/29
報告時間: 17:10/18:00
報告學生: 陳韋靜
講評老師: 吳佳慶
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/991029-3.pdf

Wnt activity defines colon cancer stem cells and is regulated by the microenviroment

Nature cell biology. 2010 May; 12(5):468-76.

 

Speaker : 陳韋靜

Commentator :吳佳慶 老師

Date: 2010.10.29

Room: 602

 

Abstract

   The Wnt signaling pathway has an important role in embryogenesis and caner. When Wnt bind to their receptor, the β-catenin was translocated into the nucleus. When the APC was mutated, it resulted in a defective β-catenin degradation complex and accumulated the β-catenin in the nucleus. However, the immunohistochemical studies have revealed that colon carcinomas harbouring APC mutations do not contain nuclear β-catenin homogeneously. The phenomena are intriguing in the light of the cancer stem cells (CSCs), which are endowed with tumorigenic ability, whereas most tumor cells have undergone differentiation and lost their tumorigenic potential. Therefore, the author proposed a preponderant role for this pathway in colon CSCs as well. The colon cancer spheroidal cultures were transduced lentivirally with the TOP–GFP or CMV–GFP or PGK–GFP constructs. The author found that the Wnt activity was heterogeneity. Aditionally, the stem-cell-associated Wnt target genes were predominantly upregulated in the TOP–GFPhigh fraction, whereas genes associated with epithelial diffrentiation were clearly enhanced in the TOP–GFPlow fraction. In order to study whether the CSC can be characterized by high expression levels of Wnt, the author assay the clonogenic potential of the TOP–GFPhigh and TOP–GFPlow fraction and transplant the cell into the NOD/SCID IL-2 receptor gamma chain null mice. Furthermore, the author found that the myofibroblast can support CSC properties and regulate Wnt signaling by secreting the hepatocyte growth factor (HGF). Therefore, the author propose that stemness of colon cancer cells is in part orchestrated by the microenvironment and is a much more dynamic quality than previously expected that can be defined by high Wnt activity.

 

References

Brabletz T. et al. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10356-61.