Loss of p53 epigenetically modulates epithelial to mesenchymal transition in colorectal cancer

Transl Oncol. 2024 Feb 26;43:101848. doi: 10.1016/j.tranon.2023.101848. Online ahead of print.ABSTRACTEpithelial to Mesenchymal transition (EMT) drives cancer metastasis and is governed by genetic and epigenetic alterations at multiple levels of regulation. It is well established that loss/mutation of p53 confers oncogenic function to cancer cells and promotes metastasis. Though transcription factors like ZEB1, SLUG, SNAIL and TWIST have been implied in EMT signalling, p53 mediated alterations in the epigenetic machinery accompanying EMT are not clearly understood. This work attempts to explore epigenetic signalling during EMT in colorectal cancer (CRC) cells with varying status of p53. Towards this, we have induced EMT using TGFβ on CRC cell lines with wild type, null and mutant p53 and have assayed epigenetic alterations after EMT induction. Transcriptomic profiling of the four CRC cell lines revealed that the loss of p53 confers more mesenchymal phenotype with EMT induction than its mutant counterparts. This was also accompanied by upregulation of epigenetic writer and eraser machinery suggesting an epigenetic signalling cascade triggered by TGFβ signalling in CRC. Significant agonist and antagonistic relationships observed between EMT factor SNAI1 and SNAI2 with epigenetic enzymes KDM6A/6B and the chromatin organiser SATB1 in p53 null CRC cells suggest a crosstalk between epigenetic and EMT factors. The observed epigenetic regulation of EMT factor SNAI1 correlates with ...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Source Type: research