Discovery of non-genomic drivers of YAP signaling modulating the cell plasticity in CRC tumor lines
March 13, 2024
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 chemoresistance, which could be potentially resolved by targeting the underlying YAP regulatory elements, a potential target of CRC treatment.
Keywords: Cancer; Classification Description; Stem cell plasticity; Transcriptomics.
Keywords: Cancer; Classification Description; Stem cell plasticity; Transcriptomics.
Journal Article
JOURNAL：iScience
TITLE：Discovery of non-genomic drivers of YAP signaling modulating the cell plasticity in CRC tumor lines
DOI:https://doi.org/10.1016/j.isci.2024.109247
TITLE：Discovery of non-genomic drivers of YAP signaling modulating the cell plasticity in CRC tumor lines
DOI:https://doi.org/10.1016/j.isci.2024.109247
Correspondence to
Shiro Yui, Associate Professor
Center for Stem Cell and Regenerative Medicine,
Institute of Research,
Tokyo Medical and Dental University(TMDU)
E-mail:yui.arm[@]tmd.ac.jp
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