Lijing Yang, Lei Tu, Shilpa Bisht, Yiqing Mao, Daniel Petkovich, Sara-Jayne Thursby, Jinxiao Liang, Nibedita Patel, Ray-Whay Chiu Yen, Tina Largent, Cynthia Zahnow, Malcolm Brock, Kathy Gabrielson, Kevan J Salimian, Stephen B Baylin, Hariharan Easwaran
Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAFV600E predominantly occurring in proximal colon cancers along with increased DNA methylation phenotype. Using mouse colon organoids, here we show that proximal and distal colon stem cells have distinct transcriptional programs that regulate stemness and differentiation. We identify that the homeobox transcription factor, CDX2, which is silenced by DNA methylation in proximal colon cancers, is a key mediator of the differential transcriptional programs...
February 15, 2024: Nature Communications