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Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and ?Sox2 expression
文章来源:    发布时间:2014-08-18    【字号:

Youhua Tan, Arash Tajik, Junwei Chen, Qiong Jia, Farhan Chowdhury, Lili Wang, Junjian Chen, Shuang Zhang, Ying Hong, Haiying Yi, Douglas C. Wu, Yuejin Zhang, Fuxiang Wei, Yeh-Chuin Poh, Jihye Seong, Rishi Singh, Li-Jung Lin, Sultan Doğanay, Yong Li, Haibo Jia et al. 

Nature Communications 5, Article number: 4619 doi:10.1038/ncomms5619,

Abstract 

  Tumour-repopulating cells (TRCs) are a self-renewing, tumorigenic subpopulation of cancer cells critical in cancer progression. However, the underlying mechanisms of how TRCs maintain their self-renewing capability remain elusive. Here we show that relatively undifferentiated melanoma TRCs exhibit plasticity in ​Cdc42-mediated mechanical stiffening, histone 3 lysine residue 9 (H3K9) methylation, ​Sox2 expression and self-renewal capability. In contrast to differentiated melanoma cells, TRCs have a low level of H3K9 methylation that is unresponsive to matrix stiffness or applied forces. Silencing H3K9 methyltransferase ​G9a or ​SUV39h1 elevates the self-renewal capability of differentiated melanoma cells in a ​Sox2-dependent manner. Mechanistically, H3K9 methylation at the ​Sox2 promoter region inhibits ​Sox2 expression that is essential in maintaining self-renewal and tumorigenicity of TRCs both in vitro and in vivo. Taken together, our data suggest that 3D soft-fibrin-matrix-mediated cell softening, H3K9 demethylation and ​Sox2 gene expression are essential in regulating TRC self-renewal. 

    

http://www.nature.com/ncomms/2014/140806/ncomms5619/full/ncomms5619.html 

Published 06 August 2014