Discovery of non-genomic drivers of YAP signaling modulating the cell plasticity in CRC tumor lines.

ABSTRACT: In normal intestines, a fetal/regenerative/revival cell state can be induced upon inflammation. This plasticity in cell fate is also one of the current topics in human colorectal cancer (CRC). To dissect the underlying mechanisms, we generated human CRC organoids with naturally selected genetic mutation profiles and exposed them to two different conditions by modulating the extracellular matrix (ECM). Among tested mutation profiles, a fetal/regenerative/revival state was induced following YAP activation via a collagen type I-enriched microenvironment. Mechanistically, YAP transcription was promoted by activating AP-1 and TEAD-dependent transcription and suppressing intestinal lineage-determining transcription via mechanotransduction. The phenotypic conversion was also involved in chemoresi

SUBMITTER: Ogasawara N 

PROVIDER: S-EPMC10910304 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature