Intestinal stem cells in intestinal homeostasis and colorectal tumorigenesis

Abstract

Colorectal cancer (CRC), one of the most common tumors in the world, is generally proposed to be generated from intestinal stem cells (ISCs). Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)-positive ISCs are located at the bottom of the crypt and harbor self-renewal and differentiation capacities, serving as the resource of all intestinal epithelial cells and CRC cells as well. Here we review recent progress in ISCs both in non-tumoral and tumoral contexts. We summarize the molecular mechanisms of ISC self-renewal, differentiation, and plasticity for intestinal homeostasis and regeneration. We also discuss the function of ISCs in colorectal tumorigenesis as cancer stem cells and summarize fate dynamic, competition, niche regulation, and remote environmental regulation of ISCs for CRC initiation and propagation. © The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press.