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

Nobuhiko Ogasawara; Yoshihito Kano; Yosuke Yoneyama; Sakurako Kobayashi; Satoshi Watanabe; Sakura Kirino; Fausto D. Velez-Bravo; Yourae Hong; Aleksandra Ostapiuk; Pavlo Lutsik; Iichiroh Onishi; Shinichi Yamauchi; Yui Hiraguri; Go Ito; Yusuke Kinugasa; Kenichi Ohashi; Mamoru Watanabe; Ryuichi Okamoto; Sabine Tejpar; Shiro Yui

iScience (Mar 2024)

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

Nobuhiko Ogasawara,
Yoshihito Kano,
Yosuke Yoneyama,
Sakurako Kobayashi,
Satoshi Watanabe,
Sakura Kirino,
Fausto D. Velez-Bravo,
Yourae Hong,
Aleksandra Ostapiuk,
Pavlo Lutsik,
Iichiroh Onishi,
Shinichi Yamauchi,
Yui Hiraguri,
Go Ito,
Yusuke Kinugasa,
Kenichi Ohashi,
Mamoru Watanabe,
Ryuichi Okamoto,
Sabine Tejpar,
Shiro Yui

Affiliations

Nobuhiko Ogasawara: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Yoshihito Kano: Department of Clinical Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Yosuke Yoneyama: Institute of Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Sakurako Kobayashi: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Satoshi Watanabe: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Sakura Kirino: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Fausto D. Velez-Bravo: Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
Yourae Hong: Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
Aleksandra Ostapiuk: Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
Pavlo Lutsik: Computational Cancer Biology and Epigenomics, Department of Oncology, KU Leuven, Leuven, Belgium
Iichiroh Onishi: Department of Diagnostic Pathology, Tokyo Medical and Dental University Hospital, Bunkyo-ku, Tokyo 113-8510, Japan
Shinichi Yamauchi: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Yui Hiraguri: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Go Ito: Advanced Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Yusuke Kinugasa: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Kenichi Ohashi: Department of Human Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Mamoru Watanabe: Advanced Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Ryuichi Okamoto: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Sabine Tejpar: Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium; Corresponding author
Shiro Yui: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan; Corresponding author

Journal volume & issue: Vol. 27, no. 3
p. 109247

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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