Mucosal ribosomal stress-induced PRDM1 promotes chemoresistance via stemness regulation

The majorities of colorectal cancer (CRC) cases are sporadic in origin and a large proportion of etiologies are associated with environmental stress responses. In response to external and internal stress, the ribosome stands sentinel and stress-driven ribosomal dysfunction triggers the cellular decision pathways via transcriptional reprogramming. In the present study, PR domain zinc finger protein (PRDM) 1, a master transcriptional regulator, was found to be closely associated with ribosomal actions in patients with CRC and the murine models. Stress-driven ribosomal dysfunction enhanced PRDM1 levels in intestinal cancer cells, which contributed to their survival and enhanced cancer cell stemness against cancer treatment. Mechanistically, PRDM1 facilitated clustering modulation of insulin-like growth factor (IGF) receptor-associated genes, which supported cancer cell growth and stemness-linked features. Ribosomal dysfunction-responsive PRDM1 facilitated signaling remodeling for the survival of tumor progenitors, providing compelling evidence for the progression of sporadic CRC. Kim and Moon find that the transcription factor PRDM1 is induced by ribosomal dysfunction in colorectal cancer (CRC) cells and associated with chemoresistance through a pathway involving IGF signaling. The authors further suggest PRDM1 promotes cancer cell stemness and survival, altogether providing insights into environmental stress-mediated signaling in CRC.