p53 regulates epithelial–mesenchymal transition and stem cell properties through modulating miRNAs

Abstract

ZEB1 is a protein of 1124 amino acids with a predicted relative molecular mass ~124K. However, in Supplementary Fig. S5 (corresponding to Fig. 4a) of our manuscript, the uncropped image of the ZEB1 immunoblot shows two bands with a relative molecular mass of 200K and 125K, respectively. Two major ZEB1 signals (M r 124K and 200K) have been observed in western blots when using different antibodies in various cell types (please see references 1-4 below). Therefore, to examine whether the bands observed in our study represent ZEB1, we knocked down ZEB1 in MCF12A control and p53 R175H mutant cells using shRNA (Fig. 1a) and siRNA (Fig. 1b). As shown in the figure to the right, both of the bands are diminished by knockdown of ZEB1, indicating that these bands are ZEB1.

MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis

“…Collectively, these data highlight the importance of miR-200c overexpression and its epigenetic regulation in metastatic CRC, which may be an important initial step that triggers the MET phenotype which ensues after EMT-mediated emigration of these neoplastic clones of CRC cells to the liver. In addition, transactivation of the miR-200 family by p5329 and a feedback loop mechanism between miR-200 family members and ZEB1 have also been proposed 13 30 31. However, the methylation status of the miR-200c promoter region did not correlate with the p53 genotype in CRC cell lines analysed in our study (online supplementary figure 1).…”

ZEB1-induced tumourigenesis requires senescence inhibition via activation of DKK1/mutant p53/Mdm2/CtBP and repression of macroH2A1

“…Wild-type p53 inhibits the EMT by direct transactivation of miR-200c, which targets ZEB1 mRNA for decay. Meanwhile, mutant p53 proteins induce an EMT 47. Accordingly, we found that si TP53 downregulated ZEB1 in SW480 cells (figure 6D).…”

“…Interestingly, wild-type and mutant p53 have been described to have opposite functions with regard to EMT 47. Wild-type p53 inhibits the EMT by direct transactivation of miR-200c, which targets ZEB1 mRNA for decay.…”

“…ZEB1 inhibits senescence and tumourigenesis and determines worse survival through subsequent activation of DKK1, mutant p53, Mdm2 and CtBP, and repression of macroH2A1. The dashed line refers to the induction of DKK1 by Wnt signalling as described in3 and the induction of ZEB1 by mutant p53 47. See main text for details.…”

Ginsenoside Rg1 attenuates invasion and migration by inhibiting transforming growth factor-β1-induced epithelial to mesenchymal transition in HepG2 cells

“…The multi-step process of metastasis includes local invasion, intravasation to the lymph and blood systems, survival in the bloodstream, extravasation from the microvessels and colonization at a secondary site (2,3). There is evidence to suggest that epithelial to mesenchymal transition (EMT) contributes to cancer progression, invasion and migration in various types of cancer (4,5). EMT is a cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells (6).…”