Soft 3D fibrin matrices downregulate FAK expression to promote self-renewal of tumor-repopulating cells

Tumor-repopulating cells (TRCs)

Wood, Adam Richard ; Wang ; Ning

关键词: Tumor-repopulating cells (TRCs);   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/88308/WOOD-THESIS-2015.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Tumor-repopulating cells are a highly tumorigenic subpopulation of cancer cells that exhibit stem cell-like properties (e.g. self-renewal). Previous reports have shown that soft 3D fibrin matrices promote self-renewal in TRCs by promoting histone 3 lysine residue 9 (H3K9) de-methylation and Sox2 expression [1]. However, the underlying mechanism(s) by which soft 3D fibrin matrices promote H3K9 de-methylation and Sox2 expression remain elusive. In this study we show that focal adhesion kinase (FAK) regulates Sox2 expression and H3K9 de-methylation through cell division control protein 42 homolog (Cdc42). In comparison to control melanoma cells, TRCs exhibit low FAK and Cdc42 expression. Overexpressing FAK or Cdc42 in TRCs cultured in soft 3D fibrin matrices promotes H3K9 methylation, decreases Sox expression, and suppresses colony growth. Knocking down FAK or Cdc42 expression in control melanoma cells promotes H3K9 de-methylation, increases Sox2 expression, and enhances colony growth in stiff 3D fibrin matrices. Overexpressing Cdc42 in FAK-knock down control melanoma cells inhibits H3K9 de-methylation.