Dual roles of ARID1A in both mucin production and secretion to restrain gastric signet ring cell carcinoma [Cut & Tag]

Signet ring cell carcinoma (SRCC) of the stomach is a subtype of gastric cancer with poor prognosis. It is characterized with unique large vacuoles of mucin and compressed nucleus, which resemble signet rings, while the underlying molecular mechanisms driving SRCC remain elusive. Here, we studied whether and how human gastric SRCC-associated ARID1A deficiency drove the disease. Gastric organoids and various mouse models of gastric cancer were applied to investigate the functions of ARID1A in SRCC tumorigenesis. Histological assays and transcriptome profiling were used to analyze the properties of SRCC models with Arid1a deficiency. Multi-omics analyses, including RNA-seq, CUT&Tag-seq and ATAC-seq, were performed to identify the molecular mechanisms of ARID1A loss in SRCC, which were further validated with in vitro and in vivo functional assays.