Unknown

Dataset Information

0

Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression.


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.

SUBMITTER: Tan Y 

PROVIDER: S-EPMC4133791 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4369399 | biostudies-literature
| S-EPMC9205030 | biostudies-literature
| S-EPMC7732485 | biostudies-literature
| S-EPMC5393192 | biostudies-literature
| S-EPMC6600935 | biostudies-literature
| S-EPMC6376184 | biostudies-literature
| S-EPMC7484801 | biostudies-literature
| S-EPMC7025566 | biostudies-literature
| S-EPMC7903329 | biostudies-literature
| S-EPMC6175826 | biostudies-other