Abstract
Systematic approaches for functionally validating cancer genes are needed since numerous genes mutated in cancer tissues have been identified from cancer genome sequencing. The mouse organoid culture system has been extensively used in the field of cancer research since mouse organoids can faithfully recapitulate the physiological behavior of the cells. Taking advantage of this, we recently described a platform for functionally validating colorectal cancer (CRC) driver genes that utilized CRISPR-Cas9 in mouse intestinal tumor organoids. In this review, we will describe how mouse organoids have been applied to CRC research and focus on how CRC genes can be validated using mouse organoids.
Highlights
Recent multi-omics studies have identified numerous genes mutated or deregulated in cancer tissues (Kim et al, 2011; Cerami et al, 2012)
The organoid culture has enabled us to assess the reponse of intestinal epithelial cells to anti-cancer drugs, growth factors, or inflammatory cytokines and analyze the detailed molecular mechanisms in vitro (Lindemans et al, 2015; De Sousa E Melo et al, 2017; Kajino-Sakamoto et al, 2021)
A recent study has performed a genome-scale CRISPR screen to identify genes that regulate Wnt-dependent renewal of gastric epithelial cells and identified Alk, Bclaf3, and Prkra as Wnt pathway regulators (Murakami et al, 2021); the data show that mouse organoids are useful for stem cell research
Summary
Laboratory of Molecular Genetics, National Cancer Center Research Institute, Tokyo, Japan. Systematic approaches for functionally validating cancer genes are needed since numerous genes mutated in cancer tissues have been identified from cancer genome sequencing. The mouse organoid culture system has been extensively used in the field of cancer research since mouse organoids can faithfully recapitulate the physiological behavior of the cells. We recently described a platform for functionally validating colorectal cancer (CRC) driver genes that utilized CRISPR-Cas in mouse intestinal tumor organoids. We will describe how mouse organoids have been applied to CRC research and focus on how CRC genes can be validated using mouse organoids. Reviewed by: Shingo Kato, Yokohama City University, Japan Kunishige Onuma, Kyoto University, Japan. Specialty section: This article was submitted to Toxicogenomics, a section of the journal
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