Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
- Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
- Tan Y; Arash Tajik; Junwei Chen; Qiong Jia; Farhan Chowdhury; Lili Wang; Junjian Chen; Shuang Zhang; Ying Hong; Haiying Yi1; Douglas C. Wu; Yuejin Zhang; Fuxiang Wei; Yeh-Chuin Poh; 성지혜; Rishi Singh; Li-Jung Lin; Sultan Dog˘anay; Yong Li; Haibo Jia; Taekjip Ha; Yingxiao Wang; Bo Huang; Ning Wang
- Issue Date
- Nature Communications
- VOL 5, NO 4619, 1-12
- 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.
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