Ian Y Luk, Laura J Jenkins, Kael L Schoffer, Irvin Ng, Janson W T Tse, Dmitri Mouradov, Stanislaw Kaczmarczyk, Rebecca Nightingale, Allan D Burrows, Robin L Anderson, Diego Arango, Higinio Dopeso, Larry Croft, Mark F Richardson, Oliver M Sieber, Yang Liao, Jennifer K Mooi, Natalia Vukelic, Camilla M Reehorst, Shoukat Afshar-Sterle, Vicki L J Whitehall, Lochlan Fennell, Helen E Abud, Niall C Tebbutt, Wayne A Phillips, David S Williams, Wei Shi, Lisa A Mielke, Matthias Ernst, Amardeep S Dhillon, Nicholas J Clemons, John M Mariadason
Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF and CDX1 in poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, and differentiation along the enterocytic lineage, leading to reduced growth and metastasis...
May 23, 2022: Cell Death and Differentiation