Genetic Alterations and Microenvironment that Drive Malignant Progression of Colorectal Cancer: Lessons from Mouse and Organoid Models

Mizuho Nakayama; Dong Wang; Sau Yee Kok; Hiroko Oshima; Masanobu Oshima

doi:10.15430/JCP.2022.27.1.1

Genetic Alterations and Microenvironment that Drive Malignant Progression of Colorectal Cancer: Lessons from Mouse and Organoid Models

J Cancer Prev. 2022 Mar 30;27(1):1-6. doi: 10.15430/JCP.2022.27.1.1.

Authors

Mizuho Nakayama^{1

2}, Dong Wang^{1

2}, Sau Yee Kok^{1

3}, Hiroko Oshima^{1

2}, Masanobu Oshima^{1

2}

Affiliations

¹ Division of Genetics, Cancer Research Institute, Kanazawa University, Japan.
² WPI Nano-Life Science Institute (Nano-LSI), Kanazawa University, Kanazawa, Japan.
³ Cancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Selangor, Malaysia.

Abstract

Comprehensive genome analyses have identified frequently mutated genes in human colorectal cancers (CRC). These include APC, KRAS, SMAD4, TP53, and FBXW7. The biological functions of the respective gene products in cell proliferation and homeostasis have been intensively examined by in vitro experiments. However, how each gene mutation or combinations of specific mutations drive malignant progression of CRC in vivo has not been fully understood. Based on the genomic information, we generated mouse models that carry multiple mutations of CRC driver genes in various combinations, and we performed comprehensive histological analyses to link genetic alteration(s) and tumor phenotypes, including liver metastasis. In this review article, we summarize the phenotypes of the respective genetic models carrying major driver mutations and discuss a possible mechanism of mutations underlying malignant progression.

Keywords: Colorectal cancer; Elastic modulus; Mutations; Organoid; Transgenic mice.

Publication types

Review