BICC1 drives pancreatic cancer stemness and chemoresistance by facilitating tryptophan metabolism.

ABSTRACT: Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells. However, the mechanisms sustaining stemness and chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we demonstrate that Bicaudal C homolog 1 (BICC1), an RNA binding protein regulating numerous cytoplasmic mRNAs, facilitates chemoresistance and stemness in PDAC. Mechanistically, BICC1 activated tryptophan catabolism in PDAC by up-regulating indoleamine 2,3-dioxygenase-1 (IDO1) expression, a tryptophan-catabolizing enzyme. Increased levels of tryptophan metabolites contribute to NAD⁺ synthesis and oxidative phosphorylation, leading to a stem cell-like phenotype. Blocking BICC1/IDO1

SUBMITTER: Sun H 

PROVIDER: S-EPMC11186499 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature