Cancer stem cell generation during epithelial-mesenchymal transition is temporally gated by intrinsic circadian clocks

摘要: Epithelial-mesenchymal transition (EMT) is a key event preceding tumor cell metastasis that increases invasiveness and cancer stem (CSC) populations. Studies suggest genes used in generating circadian rhythms also serve regulating EMT. To test the role of clocks cellular EMT events two lines were compared, one has well-established clock, C6 from rat glioma, does not, MCF-7 human breast tumor. tumorsphere cultures tested for evidence because previously reported rhythm enhancement tumorspheres shown by elevated amplitude increased expression clock gene Per2. Bioluminescence imaging Per2 revealed unconfirmed this important research model. Inducing CSC generation through monolayer oscillations size post-EMT CSC population, confirming are additional processes controlling stage progression. was verified distinct cellular morphological changes proteins OCT4, nestin, MSI1, CD133 along with EMT-related ZEB1, vimentin, TWIST. Quantifying single-cell behaviors time-lapse indicated population determined largely epithelial-like cells undergoing We then identified specific phase activation as potential target therapeutic treatments may suppress EMT, minimize CSCs, limit metastasis.